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Title:
AAV VECTORS ENCODING OXIDOREDUCTASE ENZYME AND USES THEREOF
Document Type and Number:
WIPO Patent Application WO/2024/059735
Kind Code:
A2
Abstract:
Provided are recombinant adeno-associated virus (rAAV) vectors, methods of treating an ocular condition, pharmaceutical compositions, and other compositions and methods, in which the rAAV vector comprises a polynucleotide encoding oxidoreductase enzymes. Methods of treatment may include administration to the lacrimal gland.

Inventors:
CARLSON ERIC C (US)
NAU JEFFREY ALAN (US)
Application Number:
PCT/US2023/074233
Publication Date:
March 21, 2024
Filing Date:
September 14, 2023
Export Citation:
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Assignee:
OYSTER POINT PHARMA INC (US)
International Classes:
C12N15/861; A61K31/711
Attorney, Agent or Firm:
LACAVA, Richard et al. (US)
Download PDF:
Claims:
037525.00573 CLAIMS What is claimed is: 1. A recombinant adeno-associated virus (rAAV) vector comprising an AAV capsid and an expression cassette, the expression cassette comprising a polynucleotide encoding an oxidoreductase enzyme, operatively linked to a promoter. 2. The rAAV vector of claim 1, wherein the oxidoreductase enzyme is thioredoxin (TRX). 3. The rAAV vector of claim 1, wherein the oxidoreductase enzyme is protein disulfide isomerase (PDI). 4. The rAAV vector of claim 3, wherein the polynucleotide comprises a sequence encoding an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 26. 5. The rAAV vector of claim 2, wherein the polynucleotide comprises a sequence encoding an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 25. 6. The rAAV vector of claim 2 or 5, wherein the polynucleotide comprises a sequence that is at least 95% identical to SEQ ID NO: 2 or SEQ ID NO: 28. 7. The rAAV vector of claim 3 or 4, wherein the polynucleotide comprises a sequence that is at least 95% identical to SEQ ID NO: 30. 8. The rAAV vector of any one of claims 1-7, wherein the promoter is a CMV promoter comprising the nucleotide sequence set forth in SEQ ID NO: 17. 9. The rAAV vector of any one of claim 8, wherein the expression cassette comprises the CMV promoter and a CMV enhancer. 10. The rAAV vector of any one of claims 1-9, wherein the expression cassette comprises a polyadenylation (polyA) sequence. 11. The rAAV vector of claim 10, wherein the polyA sequence is a BGH polyA sequence. 12. The rAAV vector of any one of claims 1-11, wherein the expression cassette comprises a Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE).

037525.00573 13. The rAAV vector of any one of claims 1-12, wherein the expression cassette comprises a Kozak sequence. 14. A composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 2 or SEQ ID NO: 28, and wherein the polynucleotide is linked to a promoter. 15. The rAAV vector of any one of claims 1-13, wherein the expression cassette is flanked by two inverted terminal repeats (ITRs). 16. The rAAV vector of claim 15, wherein the ITRs are AAV2 ITRs. 17. The rAAV vector of any one of claims 1-2 and 5-13 or the composition of any one of claims 14-16, wherein the expression cassette comprises a nucleotide sequence that shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 16. 18. The rAAV vector or the composition of any one of claims 1-17, wherein the AAV capsid comprises a VP3 that shares at least 95%, 98%, or 100% identity with AAV2 VP3 (SEQ ID NO: 8), AAV5 VP3 (SEQ ID NO: 10), AAV8 VP3 (SEQ ID NO: 12), or AAV9 VP3 (SEQ ID NO:14). 19. The rAAV vector or the composition of any one of claims 1-17, wherein the AAV capsid comprises a VP3 that shares at least 95%, 98%, or 100% identity with AAV9 (SEQ ID NO: 14). 20. A composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 2 or SEQ ID NO: 28, and wherein the polynucleotide is linked to a promoter. 21. A composition comprising an rAAV vector, wherein the rAAV vector comprises:

037525.00573 (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide sequence sharing at least 95% identity to SEQ ID NO: 2 or SEQ ID NO: 28. 22. The composition of claim 20 or 21, wherein the AAV capsid is AAV2. 23. The composition of claim 20 or 21, wherein the AAV capsid is AAV5. 24. The composition of claim 20 or 21, wherein the AAV capsid is AAV9. 25. The rAAV vector or the composition of any one of claims 1-24, wherein the polynucleotide comprises a sequence encoding a signal peptide. 26. A pharmaceutical composition comprising the rAAV vector or composition of any one of claims 1-25, and a pharmaceutically acceptable carrier. 27. The pharmaceutical composition of claim 26, wherein the composition comprises about 1 x 107 to about 1 x 1014 genome copies per milliliter of the rAAV vector. 28. The pharmaceutical composition of claim 26, wherein the composition comprises about 1 x 1012 to about 6.2 x 1012 genome copies per milliliter of the rAAV vector. 29. A method of treating an ocular condition in a subject in need thereof, the method comprising administering a therapeutically effective amount of the pharmaceutical composition of any one of claims 26-28 to the eye of the subject. 30. The method of claim 29, wherein the pharmaceutical composition is delivered to an ocular secretory gland of the subject. 31. The method of claim 29 or 30, wherein the pharmaceutical composition is delivered to the lacrimal gland. 32. The method of any one of claims 29-31, wherein the pharmaceutical composition is delivered to an accessory lacrimal gland. 33. The method of claim 32, wherein the accessory lacrimal gland is the meibomian glands.

037525.00573 34. The method of any one of claims 29-33, wherein the pharmaceutical composition is delivered to the trabecular meshwork. 35. The method of any one of claims 29-34, wherein about 1 x 109 to about 1 x 1010, about 1 x 1010 to about 1 x 1011, about 1 x 1011 to about 1 x 1012, about 1 x 1012 to about 1 x 1013, or about 1 x 1013 to about 1 x 1015 genome copies of the rAAV vector are administered. 36. The method of any one of claims 29-35, wherein the ocular condition is associated with increased oxidative stress. 37. The method of any one of claims 29-35, wherein the ocular condition is associated with loss of expression and/or function of one or more oxidoreductase enzymes. 38. The method of any one of claims 28-35, wherein the ocular condition is associated with loss of TRX expression and/or function. 39. The method of any one of claims 28-35, wherein the ocular condition is associated with loss of PDI expression and/or function. 40. The method of any one of claims 29-35, wherein the ocular condition is characterized by a loss of near vision. 41. The method of any one of claims 29-40, wherein the ocular condition is presbyopia. 42. The method of any one of claims 29-40, wherein the ocular condition is cataract formation. 43. The method of any one of claims 29-40, wherein the ocular condition is ocular hypertension. 44. The method of any one of claims 29-40, wherein the ocular condition is meibomian gland dysfunction (MDI). 45. The method of any one of claims 29-40, wherein the ocular condition is glaucoma. 46. The method of any one of claims 29-45, wherein the method results in expression of the oxidoreductase enzyme in the cells of the lacrimal gland and/or an accessory lacrimal gland, and/or in the trabecular meshwork.

037525.00573 47. The method of any one of claims 29-46, wherein the method results in expression of TRX in the cells of the lacrimal gland and/or an accessory lacrimal gland, and/or in the trabecular meshwork. 48. The method of any one of claims 29-47, wherein the method results in secretion of TRX into the tear film and/or onto the ocular surface of the subject. 49. The method of any one of claims 29-48, wherein the method results in an improvement of one or more symptoms of the ocular condition. 50. The method of anyone of claims 29-49, wherein the method results in an improvement of visual acuity. 51. The method of any one of claims 29-50, wherein the method results in a reduced need for corrective lenses. 52. The method of any one of claims 29-51, wherein the method results in a delay of the progression of the condition. 53. The method of claim 52, wherein the method results in the progression of the condition in the subject being delayed by about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to about 80%, about 80% to about 90%, about 90% to about 95% or by more than about 95% compared to a control subject. 54. The method of any one of claim 29-53, wherein the method results in the onset of the condition being delayed by about 6 months to about 12 months, about 12 months to about 18 months, about 18 months to about 24 months, about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or by more than 20 years compared to a control subject. 55. The method of claim 53 or 54, wherein the control subject is an age-matched subject who is not treated with an rAAV vector comprising an expression cassette, the expression cassette comprising a polynucleotide encoding TRX.

037525.00573 56. The method of any one of claims 29-55, wherein the subject requires corrective lenses prior to the administration of the rAAV, and the administration results in an unchanged requirement for the strength of the corrective lenses for at least about 6 months to about 12 months, about 12 months to about 18 months, about 18 months to about 24 months, about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or for more than 20 years after administration of the rAAV. 57. The method of any one of claims 29-55, wherein the visual acuity of the subject remains unchanged for at least about 6 months to about 9 months, about 9 months to about 12 months, about 12 months to about 15 months, about 15 months to about 18 months, about 18 months to about 21 months, about 21 months to about 24 months, to about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or for more than 20 years after the administration of the rAAV vector 58. The method of any one of claims 29-57, wherein the method further comprises administering one or more additional therapeutic agents. 59. The method of any one of claims 29-58, wherein the subject is human. 60. The pharmaceutical composition of any one of claims 26-28 for use in a method of treating an ocular condition in a subject in need thereof comprising administering an effective amount of the pharmaceutical composition to the eye of the subject. 61. The pharmaceutical composition of any one of claims 26-28 for use in the manufacture of a medicament for treating an ocular condition in a subject in need thereof. 62. A compound for use in treating an ocular condition in a subject, comprising administering the composition or rAAV of any one of claims 1-25 or the pharmaceutical composition of rAAV vector of any one of claims 26-28, and a pharmaceutically acceptable carrier.

037525.00573 63. A kit comprising an rAAV vector or composition of any one of claims 1-25 or the pharmaceutical composition of any one of claims 26-28, and a pharmaceutically acceptable carrier, and instructions for use in treating an ocular condition in a subject, comprising administering the pharmaceutical composition to the eye of the subject. 64. A kit comprising an rAAV vector or composition of any one of claims 1-25 or the pharmaceutical composition of any one of claims 26-28, and a pharmaceutically acceptable carrier, and instructions for use in treating presbyopia in a subject, comprising administering the pharmaceutical composition to the eye of the subject. 65. A kit comprising an rAAV vector or composition of any one of claims 1-25 or the pharmaceutical composition of any one of claims 26-28, and a pharmaceutically acceptable carrier, and instructions for use in treating cataract formation in a subject, comprising administering the pharmaceutical composition to the eye of the subject. 66. A kit comprising an rAAV vector or composition of any one of claims 1-25 or the pharmaceutical composition of any one of claims 26-28, and a pharmaceutically acceptable carrier, and instructions for use in treating loss of accommodation in a subject, comprising administering the pharmaceutical composition to the eye of the subject. 67. A kit comprising an rAAV vector or composition of any one of claims 1-25 or the pharmaceutical composition of any one of claims 26-28, and a pharmaceutically acceptable carrier, and instructions for use in treating ocular hypertension in a subject, comprising administering the pharmaceutical composition to the eye of the subject. 68. A kit comprising an rAAV vector or composition of any one of claims 1-25 or the pharmaceutical composition of any one of claims 26-28, and a pharmaceutically acceptable carrier, and instructions for use in treating meibomian gland dysfunction (MGD) in a subject, comprising administering the pharmaceutical composition to the eye of the subject. 69. A pharmaceutical composition, comprising a) a polypeptide comprising an oxidoreductase enzyme, or a fragment thereof, optionally wherein the polypeptide has an amino acid sequence having at least 90% identity to an amino acid sequence selected from SEQ ID NO: 1 and 26; and

037525.00573 b) a pharmaceutically-acceptable carrier suitable for administration to an eye of a human subject. 70. A pharmaceutical composition, comprising a) a vector comprising a polynucleotide that encodes a polypeptide comprising an oxidoreductase enzyme, or a fragment thereof, optionally wherein the polypeptide has an amino acid sequence having at least 90% identity to an amino acid sequence selected from SEQ ID NO: 1 and 26; and b) a pharmaceutically-acceptable carrier suitable for administration to an eye of a human subject. 71. The pharmaceutical composition of claims 69 or 70, wherein the pharmaceutically- acceptable carrier comprises water; sterile water; pyrogen-free water; phosphate-buffered saline; HEPES-buffered saline; an isotonic sodium chloride solution; a balanced salt solution; a wetting agent; a surfactant; a tonicity agent; a pH modifier; a viscosity-modifying agent; a buffering agent; a disaccharide, optionally, sucrose or trehalose; a cellulose and/or a derivate thereof; an amino acid, optionally histidine; or any combination thereof. 72. The pharmaceutical composition of any one of claims 69-71, wherein the polypeptide has at least 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 26. 73. The pharmaceutical composition of any one of claims 69-72, wherein the polypeptide comprises at least 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, or 500 amino acids. 74. The pharmaceutical composition of any one of claims 69-73, wherein the formulation is a liquid formulated for application to an ocular surface, or into an ocular surface, or for intralacrimal injection, of the eye of the human subject. 75. The pharmaceutical composition of any one of claims 70-74, comprising the vector, wherein the vector is present in the composition in an amount effective to express from 100

037525.00573 pg/mL to 50 µg/mL of the polypeptide in a tear film of a subject subsequent to administration of the composition to the subject. 76. The pharmaceutical composition of any one of claims 70-75, comprising the vector, wherein the polynucleotide is operably linked to a promoter. 77. The pharmaceutical composition of any one of claims 70-76, comprising the vector, wherein the vector is engineered to constitutively express the polypeptide having an amino acid sequence having at least 90% identity to an amino acid sequence selected from SEQ ID NO: 1 and 26. 78. The pharmaceutical composition of any one of claims 70-77, comprising the vector, wherein the vector comprises a virus, optionally an adenoviral vector or a lentiviral vector; a plasmid; an episome; or an artificial chromosome; and optionally comprises one or more lipids, polycations, DNA-carrier proteins, histones, pseudocapsids, chimeric proteins, or endocytosis receptor proteins. 79. The pharmaceutical composition of any one of claims 69, or 71-74, comprising the polypeptide, wherein the polypeptide is present in the pharmaceutical composition at a concentration of 100 pg/mL to 50 µg/mL. 80. The pharmaceutical composition of any one of claims 69, 71-74, or 79, comprising the polypeptide, wherein the polypeptide is present in the pharmaceutical composition in an amount of 500 ng to 5 µg. 81. The pharmaceutical composition of any one of claims 69, 71-74, 79, or 80, comprising the polypeptide, wherein the polypeptide is present in the pharmaceutical composition in a unit dose amount. 82. A method of treating an ocular disease, disorder, or condition in a subject in need thereof, the method comprising administering an effective amount of the pharmaceutical composition of any one of claims 69-81 to an eye of the subject.

037525.00573 83. The method of claim 82, wherein the pharmaceutical composition is delivered to an accessory lacrimal gland. 84. The method of claim 83, wherein the accessory lacrimal gland is the meibomian glands. 85. The method of any one of claims 82-84, wherein the pharmaceutical composition is delivered to the trabecular meshwork. 86. The method of any one of claims 82-85, wherein the ocular condition is: a) associated with increased oxidative stress; b) associated with loss of expression and/or function of one or more oxidoreductase enzymes; c) associated with loss of TRX expression and/or function; and/or d) associated with loss of PDI expression and/or function. 87. The method of any one of claims 82-86, wherein the ocular condition is characterized by a loss of near vision. 88. The method of any one of claims 82-87, wherein the ocular condition is: a) presbyopia; b) cataract formation; c) ocular hypertension; d) meibomian gland dysfunction (MDI); and/or e) glaucoma. 89. The method of any one of claims 82-88, wherein the method results in: a) expression of the oxidoreductase enzyme in the cells of the lacrimal gland and/or an accessory lacrimal gland, and/or in the trabecular meshwork; b) expression of TRX in the cells of the lacrimal gland and/or an accessory lacrimal gland, and/or in the trabecular meshwork; and/or c) secretion of TRX into the tear film and/or onto the ocular surface of the subject. 90. The method of any one of claims 82-88, wherein the method results in:

037525.00573 a) an improvement of one or more symptoms of the ocular condition; b) an improvement of visual acuity; c) a reduced need for corrective lenses; and/or d) a delay of the progression of the ocular condition. 91. The method of any one of claims 82-88, wherein the method results in the progression of the ocular condition in the subject being delayed by about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to about 80%, about 80% to about 90%, about 90% to about 95% or by more than about 95% compared to a control subject. 92. The method of any one of claims 82-91, wherein the administration results in expression of a functional oxidoreductase enzyme in one or more cells of a lacrimal gland and/or an accessory lacrimal gland of the subject. 93. The method of any one of claims 82-92, wherein the administration results in secretion of a functional oxidoreductase enzyme into a tear film of the subject. 94. The method of claim 93, wherein secretion of the functional oxidoreductase enzyme into the tear film is stimulated by a cholinergic agonist. 95. The method of any one of claims 82-94, wherein the administration is to an ocular surface, or into an ocular surface of the subject, and/or to a lacrimal gland of the subject. 96. The method of any one of claims 82-95, wherein the symptom is selected from the group consisting of itching, swelling, tearing, and redness. 97. The method of any one of claims 82-96, wherein the administration results in an improvement of 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, 3 point, 3.5 points, or 4 points on the Conjunctival Itching Grading Scale. 98. The method of any one of claims 82-97, wherein the subject is a human subject.

037525.00573 99. A kit comprising the pharmaceutical composition of any one of claims 69-81 and instructions for use in treating a condition in a human subject, wherein the instructions comprise administering the pharmaceutical composition to an eye of the human subject. 100. The pharmaceutical composition of any one of claims 69-81 for use in the manufacture of a medicament for treating a condition in a human subject in need thereof. 101. A pharmaceutical composition according to any of claims 26 to 28 for use in a method of treatment according to any of claims 29 to 59. 102. A pharmaceutical composition according to any of claims 69 to 81 for use in a method of treatment according to any of claims 82 to 98.

Description:
037525.00573 AAV VECTORS ENCODING OXIDOREDUCTASE ENZYME AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of the priority date of U.S. Provisional Patent Application Nos.63/375,613, filed on September 14, 2022, and 63/383,055, filed on November 9, 2022, the disclosures of which are incorporated by reference herein in their entirety. REFERENCE TO SEQUENCE LISTING [0002] The contents of the electronic sequence listing (OYST_028_03WO_SeqList_ST26 .xml (56 KB), which was created on September 9, 2023, is herein incorporated by reference in its entirety. BACKGROUND [0003] The thioredoxin system is a highly conserved redox system which plays a key role in maintaining the reduced environment of the cell. Thioredoxin (TRX) is a major, ubiquitous disulfide reductase which is reduced by thioredoxin reductase (TRXR) which transfers electrons from NAPDH to TRX. See Arner and Holmgren, Eur. J. Biochem. 267, 6102-6109 (2000). Thiol-disulfide exchange reactions control protein function via the redox state of structural or catalytic SH groups. Oxidation of a critical SH group will generally lead to a changed biological function of a protein. Thus, thiol redox control is a major regulatory mechanism in signal transduction and increased production of reactive oxygen species oxidizing protein thiols and its balance by thioredoxin and glutathione glutaredoxin-dependent reactions have a wide range of functions in cellular physiology and pathological conditions (Arner and Holmgren 2000). [0004] The thioredoxin system in the lens of the eye has been shown to gradually weaken with age (Xing and Lou, Invest Ophthalmol Vis Sci.2010 Dec; 51(12): 6598–6604), and production of reactive oxygen species and reduction of endogenous antioxidants both contribute to cataract formation. [0005] A related oxidoreductase is protein disulfide isomerase (PDI). The first reported discovery of PDI occurred in 1963 and it was thought to function as a chaperone for protein- folding (Goldberger, R.F. et.al., J.Biol. Chem 1963; 238; 628-635). A common response to 037525.00573 stress is the misfolding of proteins, which PDI serves as a critical defense against. Functionally, PDI is also able to reduce, form and rearrange disulfide bonds as further support for maintaining protein structural integrity, which supports the localization of this 58 kilodalton Calcium- binding chaperone protein in the endoplasmic reticulum (ER). The catalytic activities of PDI, including thiol oxidation/reduction, disulfide isomerization, and redox-regulated chaperon activity are central to ER function (Maattanen, et al (2010) Semin Cell Dev Biol 21:500-11). [0006] Presbyopia is a common ocular disorder, affecting millions of people worldwide, especially those above 40 years of age. It is predicted that 1.8 billion individuals will be affected by presbyopia by 2050 (Grzybowski et al., Asia Pac J Ophthalmol (Phila) 2020;9:226– 233). Presbyopia is caused by a decrease in lens flexibility. [0007] Medical treatment of ocular conditions that affect the human lens, such as cataract formation and/or presbyopia are known. Medical treatment often includes prescription lenses to allow for near vision due to the loss of elasticity of the human lens. Surgical treatment often includes removal of the natural human lens and replacement with an intraocular lens. [0008] In addition, pharmacological treatments for presbyopia are being studied. Such pharmacological treatments predominantly work by exerting a pinhole effect and increasing the depth of field (e.g., NSAIDs, parasympathomimetics, or COX2 inhibitors) or to soften the lens (e.g., EV06, a lipoic acid choline ester), with limited success (Grybowski 2020). [0009] Despite available treatments these ocular conditions remain a challenge for ophthalmologists and therapeutic strategies start with vision correction to account for loss of accommodation and visual acuity, and often result in surgical removal of the lens. [0010] Improvement to medical treatment of human lens aging and disorders would be desirable, and there remains an unmet clinical need for long-term, effective treatments of presbyopia and other ocular diseases. [0011] Munemasa, Y., Ahn, J. H., Kwong, J. M. K., Caprioli, J., & Piri, N. (2009). Redox proteins thioredoxin 1 and thioredoxin 2 support retinal ganglion cell survival in experimental glaucoma. Gene Therapy, 16(1), 17-25. [0012] Despite available treatments these ocular conditions remain a challenge for ophthalmologists and therapeutic strategies start with vision correction to account for loss of accommodation and visual acuity, and often result in surgical removal of the lens. [0013] Improvement to medical treatment of human lens aging and disorders would be desirable, and there remains an unmet clinical need for long-term, effective treatments of presbyopia and other ocular diseases. 037525.00573 SUMMARY OF THE DISCLOSURE [0014] In some aspects, the disclosure provides a recombinant adeno-associated virus (rAAV) vector comprising an AAV capsid and an expression cassette, the expression cassette comprising a polynucleotide encoding an oxidoreductase enzyme, operatively linked to a promoter. [0015] In some embodiments, the oxidoreductase enzyme is thioredoxin (TRX). In some embodiments, the oxidoreductase enzyme is protein disulfide isomerase (PDI). In some embodiments, the polynucleotide comprises a sequence encoding an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 26. In some embodiments, the polynucleotide comprises a sequence encoding an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 25. [0016] In some embodiments, the polynucleotide comprises a sequence that is at least 95% identical to SEQ ID NO: 2 or SEQ ID NO: 28. In some embodiments, the polynucleotide comprises a sequence that is at least 95% identical to SEQ ID NO: 2. In some embodiments, the polynucleotide comprises a sequence that is at least 95% identical to SEQ ID NO: 28. In some embodiments, the polynucleotide comprises a sequence that is at least 95% identical to SEQ ID NO: 24. In some embodiments, the polynucleotide comprises a sequence that is at least 95% identical to SEQ ID NO: 30. [0017] In some embodiments, the promoter is a CMV promoter comprising the nucleotide sequence set forth in SEQ ID NO: 17. [0018] In some embodiments, the expression cassette comprises the CMV promoter and a CMV enhancer. In some embodiments, the expression cassette comprises a polyadenylation (polyA) sequence. In some embodiments, the polyA sequence is a BGH polyA sequence. [0019] In some embodiments, the expression cassette comprises a Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE). In some embodiments, the expression cassette comprises a Kozak sequence. [0020] In some embodiments, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 2 or SEQ ID NO: 28, and wherein the polynucleotide is linked to a promoter. [0021] In some embodiments, the disclosure provides a composition comprising an rAAV 037525.00573 vector, wherein the rAAV vector comprises: (a) an AAV capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 2, and wherein the polynucleotide is linked to a promoter. [0022] In some embodiments, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 28, and wherein the polynucleotide is linked to a promoter. [0023] In some embodiments, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 30, and wherein the polynucleotide is linked to a promoter. [0024] In some embodiments, the expression cassette is flanked by two inverted terminal repeats (ITRs). In some embodiments, the ITRs are AAV2 ITRs. [0025] In some embodiments, the expression cassette comprises a nucleotide sequence that shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 16. [0026] In some embodiments, the AAV capsid comprises a VP3 that shares at least 95%, 98%, or 100% identity with AAV2 VP3 (SEQ ID NO: 8), AAV5 VP3 (SEQ ID NO: 10), AAV8 VP3 (SEQ ID NO: 12), or AAV9 VP3 (SEQ ID NO: 14). In some embodiments, the AAV capsid comprises a VP3 that shares at least 95%, 98%, or 100% identity with AAV9 (SEQ ID NO: 14). [0027] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 2 or SEQ ID NO: 28, and wherein the polynucleotide is linked to a promoter. [0028] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide 037525.00573 comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 2, and wherein the polynucleotide is linked to a promoter. [0029] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 28, and wherein the polynucleotide is linked to a promoter. [0030] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 30, and wherein the polynucleotide is linked to a promoter. [0031] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide sequence sharing at least 95% identity to SEQ ID NO: 2 or SEQ ID NO: 28. [0032] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide sequence sharing at least 95% identity to SEQ ID NO: 2. [0033] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide sequence sharing at least 95% identity to SEQ ID NO: 28. [0034] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide sequence sharing at least 95% identity to SEQ ID NO: 30. [0035] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an rAAV2/1, rAAV2/3, rAAV2/4, rAAV2/5, rAAV2/6, rAAV2/7, rAAV2/8, or rAAV2/9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing 037525.00573 at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 2 or SEQ ID NO: 28, and wherein the polynucleotide is linked to a promoter. [0036] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an rAAV2/1, rAAV2/3, rAAV2/4, rAAV2/5, rAAV2/6, rAAV2/7, rAAV2/8, or rAAV2/9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 2, and wherein the polynucleotide is linked to a promoter. [0037] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an rAAV2/1, rAAV2/3, rAAV2/4, rAAV2/5, rAAV2/6, rAAV2/7, rAAV2/8, or rAAV2/9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 28, and wherein the polynucleotide is linked to a promoter. [0038] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an rAAV2/1, rAAV2/3, rAAV2/4, rAAV2/5, rAAV2/6, rAAV2/7, rAAV2/8, or rAAV2/9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 30, and wherein the polynucleotide is linked to a promoter. [0039] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an rAAV2/1, rAAV2/3, rAAV2/4, rAAV2/5, rAAV2/6, rAAV2/7, rAAV2/8, or rAAV2/9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide sequence sharing at least 95% identity to SEQ ID NO: 2 or SEQ ID NO: 28. [0040] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an rAAV2/1, rAAV2/3, rAAV2/4, rAAV2/5, rAAV2/6, rAAV2/7, rAAV2/8, or rAAV2/9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide sequence sharing at least 95% identity to SEQ ID NO: 2. [0041] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an rAAV2/1, rAAV2/3, rAAV2/4, rAAV2/5, rAAV2/6, rAAV2/7, rAAV2/8, or rAAV2/9 capsid, and (b) an expression cassette, wherein 037525.00573 the expression cassette comprises a polynucleotide sequence sharing at least 95% identity to SEQ ID NO: 28. [0042] In another embodiment, the disclosure provides a composition comprising an rAAV vector, wherein the rAAV vector comprises: (a) an rAAV2/1, rAAV2/3, rAAV2/4, rAAV2/5, rAAV2/6, rAAV2/7, rAAV2/8, or rAAV2/9 capsid, and (b) an expression cassette, wherein the expression cassette comprises a polynucleotide sequence sharing at least 95% identity to SEQ ID NO: 30. [0043] In some embodiments, the AAV capsid is AAV2. In some embodiments, the AAV capsid is AAV5. In some embodiments, the AAV capsid is AAV9. [0044] In some embodiments, the polynucleotide comprises a sequence encoding a signal peptide. [0045] In some embodiments, the disclosure provides a pharmaceutical composition comprising the rAAV vector or composition of any one of the aspects and embodiments described herein, and a pharmaceutically acceptable carrier. [0046] In some embodiments, the composition comprises about 1 x 10 7 to about 1 x 10 14 genome copies per milliliter of the rAAV vector. In some embodiments, the composition comprises about 1 x 10 12 to about 6.2 x 10 12 genome copies per milliliter of the rAAV vector. [0047] In some embodiments, the disclosure provides a method of treating an ocular condition in a subject in need thereof, the method comprising administering a therapeutically effective amount of the pharmaceutical composition of any one of the embodiments described herein to the eye of the subject. [0048] In some embodiments, the pharmaceutical composition is delivered to an ocular secretory gland of the subject. In some embodiments, the pharmaceutical composition is delivered to the lacrimal gland. In some embodiments, the pharmaceutical composition is delivered to an accessory lacrimal gland. In some embodiments, the accessory lacrimal gland is the meibomian glands. In some embodiments, the pharmaceutical composition is delivered to the trabecular meshwork. [0049] In some embodiments, about 1 x 10 9 to about 1 x 10 10 , about 1 x 10 10 to about 1 x 10 11 , about 1 x 10 11 to about 1 x 10 12 , about 1 x 10 12 to about 1 x 10 13 , or about 1 x 10 13 to about 1 x 10 15 genome copies of the rAAV vector are administered. [0050] In some embodiments, the ocular condition is associated with increased oxidative stress. In some embodiments, the ocular condition is associated with loss of expression and/or function of one or more oxidoreductase enzymes. In some embodiments, the ocular condition 037525.00573 is associated with loss of TRX expression and/or function. In some embodiments, the ocular condition is associated with loss of PDI expression and/or function. In some embodiments, the ocular condition is characterized by a loss of near vision. In some embodiments, the ocular condition is presbyopia. In some embodiments, the ocular condition is cataract formation. In some embodiments, the ocular condition is ocular hypertension. In some embodiments, the ocular condition is meibomian gland dysfunction (MDI). In some embodiments, the ocular condition is glaucoma. [0051] In some embodiments, the method results in expression of the oxidoreductase enzyme in the cells of the lacrimal gland and/or an accessory lacrimal gland, and/or in the trabecular meshwork. In some embodiments, the method results in expression of TRX and/or PDI in the cells of the lacrimal gland and/or an accessory lacrimal gland, and/or in the trabecular meshwork. [0052] In some embodiments, the method results in secretion of TRX and/or PDI into the tear film and/or onto the ocular surface of the subject. [0053] In some embodiments, secretion of TRX and/or PDI into the tear film is stimulated by administration of an electrical stimulus, mechanical stimulus, ultrasound stimulus, and/or a drug. An example of an electrical stimulus is an intranasal stimulator such as the TrueTear® Intranasal Tear Neurostimulator. An example of a mechanical stimulus is oscillatory energy provided by a device such as the iTEAR®100. An example of an ultrasound stimulus is application of a neuromodulation device, like the iTear system (Olympic Ophthalmics) developed to treat dry eye disease. In some embodiments, the drug that stimulates secretion of TRX and/or PDI into the tear film is a cholinergic agonist (e.g., pilocarpine or cevimeline). In some embodiments, the drug is a nicotinic acetylcholine receptor (nAChR) agonist (e.g., varenicline). In some embodiments, the drug is a secretagogue or mucoprotective agent (e.g., diquafosol, rebamipide, or ecabet). In some embodiments, the drug that stimulates secretion of TRX and/or PDI into the tear film is administered into the eye. In some embodiments the drug, such as the cholinergic agonist, is administered orally. In some embodiments, secretion of TRX and/or PDI into the tear film is stimulated by a drug, such as a cholinergic agonist or nAChR agonist, administered into the nasal cavity. In some embodiments, an rAAV vector, or any other construct configured to express TRX and/or PDI described herein, may be administered to a subject as a co-therapy in combination with a tear-increasing stimulus and/or drug (e.g., those described in this paragraph). In some embodiments, such co-therapies may follow any 037525.00573 protocol, or use any components or parameters, described in International Patent Application Pub. No. WO 2022/235786, the entire contents of which is incorporated herein. [0054] In some embodiments, the method results in an improvement of one or more symptoms of the ocular condition. In some embodiments, the method results in an improvement of visual acuity. In some embodiments, the method results in a reduced need for corrective lenses. In some embodiments, the method results in a delay of the progression of the condition. [0055] In some embodiments, the method results in the progression of the condition in the subject being delayed by about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to about 80%, about 80% to about 90%, about 90% to about 95% or by more than about 95% compared to a control subject. [0056] In some embodiments, the method results in the onset of the condition being delayed by about 6 months to about 12 months, about 12 months to about 18 months, about 18 months to about 24 months, about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or by more than 20 years compared to a control subject. [0057] In some embodiments, the control subject is an age-matched subject who is not treated with an rAAV vector comprising an expression cassette, the expression cassette comprising a polynucleotide encoding TRX. [0058] In some embodiments, the subject requires corrective lenses prior to the administration of the rAAV, and the administration results in an unchanged requirement for the strength of the corrective lenses for at least about 6 months to about 12 months, about 12 months to about 18 months, about 18 months to about 24 months, about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or for more than 20 years after administration of the rAAV. [0059] In some embodiments, the visual acuity of the subject remains unchanged for at least about 6 months to about 9 months, about 9 months to about 12 months, about 12 months to about 15 months, about 15 months to about 18 months, about 18 months to about 21 months, about 21 months to about 24 months, to about 2 years to about 3 years, about 3 years to about 037525.00573 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or for more than 20 years after the administration of the rAAV vector [0060] In some embodiments, the method further comprises administering one or more additional therapeutic agents. In some embodiments, the additional therapeutic agent that increases tear production is a cholinergic agonist. [0061] In some embodiments, the subject is human. [0062] In some embodiments, the disclosure provides a pharmaceutical composition of any of the aspects and embodiments described herein for use in a method of treating an ocular condition in a subject in need thereof comprising administering an effective amount of the pharmaceutical composition to the eye of the subject. [0063] In some embodiments, the disclosure provides a pharmaceutical composition of any of the aspects and embodiments described herein for use in the manufacture of a medicament for treating an ocular condition in a subject in need thereof. [0064] In some embodiments, the disclosure provides a pharmaceutical composition for use in treating an ocular condition in a subject, wherein the pharmaceutical composition comprises a vector, such as any rAAV vector as described herein, encoding an oxidoreductase as described herein and a pharmaceutically acceptable carrier. [0065] In some embodiments, the disclosure provides a kit comprising an rAAV vector or composition of any of the aspects and embodiments described herein, and a pharmaceutically acceptable carrier, and instructions for use in treating an ocular condition in a subject, comprising administering the pharmaceutical composition to the eye of the subject. [0066] In some embodiments, the disclosure provides a kit comprising an rAAV vector or composition of any one of the aspects and embodiments described herein, and a pharmaceutically acceptable carrier, and instructions for use in treating presbyopia in a subject, comprising administering the pharmaceutical composition to the eye of the subject. [0067] In some embodiments, the disclosure provides a kit comprising an rAAV vector or composition of any of the aspects and embodiments described herein, and a pharmaceutically acceptable carrier, and instructions for use in treating cataract formation in a subject, comprising administering the pharmaceutical composition to the eye of the subject. [0068] In some embodiments, the disclosure provides a kit comprising an rAAV vector or composition of any of the aspects and embodiments described herein, and a pharmaceutically 037525.00573 acceptable carrier, and instructions for use in treating loss of accommodation in a subject, comprising administering the pharmaceutical composition to the eye of the subject. [0069] In some embodiments, the disclosure provides a kit comprising an rAAV vector or composition of any or the aspects and embodiments described herein, and a pharmaceutically acceptable carrier, and instructions for use in treating ocular hypertension in a subject, comprising administering the pharmaceutical composition to the eye of the subject. [0070] In some embodiments, the disclosure provides a kit comprising an rAAV vector or composition of any of the aspects and embodiments described herein, and a pharmaceutically acceptable carrier, and instructions for use in treating meibomian gland dysfunction (MGD) in a subject, comprising administering the pharmaceutical composition to the eye of the subject. [0071] In some embodiments, the disclosure provides a pharmaceutical composition, comprising a) a polypeptide comprising an oxidoreductase enzyme, or a fragment thereof, optionally wherein the polypeptide has an amino acid sequence having at least 90% identity to an amino acid sequence selected from SEQ ID NO: 1 and 26; and b) a pharmaceutically acceptable carrier suitable for administration to an eye of a human subject. [0072] In some embodiments, the disclosure provides a pharmaceutical composition, comprising a) a vector comprising a polynucleotide that encodes a polypeptide comprising an oxidoreductase enzyme, or a fragment thereof, optionally wherein the polypeptide has an amino acid sequence having at least 90% identity to an amino acid sequence selected from SEQ ID NO: 1 and 26; and b) a pharmaceutically acceptable carrier suitable for administration to an eye of a human subject. [0073] In some embodiments, the pharmaceutically-acceptable carrier comprises water; sterile water; pyrogen-free water; phosphate-buffered saline; HEPES-buffered saline; an isotonic sodium chloride solution; a balanced salt solution; a wetting agent; a surfactant; a tonicity agent; a pH modifier; a viscosity-modifying agent; a buffering agent; a disaccharide, optionally, sucrose or trehalose; a cellulose and/or a derivate thereof; an amino acid, optionally histidine; or any combination thereof. [0074] In some embodiments, the polypeptide has at least 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 26. [0075] In some embodiments, the polypeptide comprises at least 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, or 500 amino acids. 037525.00573 [0076] In some embodiments, the formulation is a liquid formulated for application to an ocular surface, or into an ocular surface, or for intralacrimal injection, of the eye of a human subject. [0077] In some embodiments, the pharmaceutical composition comprises an rAAV vector, wherein the vector is present in the composition in an amount effective to express from 100 pg/mL to 50 µg/mL of the polypeptide (e.g., TRX1 or PDI) in a tear film of a subject subsequent to administration of the composition to a subject. [0078] In some embodiments, the polynucleotide encoding TRX1 and/or PDI is operably linked to a promoter. [0079] In some embodiments, a pharmaceutical composition comprises an rAAV vector, wherein the rAAV vector is engineered to constitutively express a polypeptide having an amino acid sequence having at least 90% identity to an amino acid sequence selected from SEQ ID NO: 1 and 26. [0080] In some embodiments, an rAAV vector as described herein comprises a virus, optionally an adenoviral vector or a lentiviral vector; a plasmid; an episome; or an artificial chromosome; and optionally comprises one or more lipids, polycations, DNA-carrier proteins, histones, pseudocapsids, chimeric proteins, or endocytosis receptor proteins. [0081] In some embodiments, a pharmaceutical composition comprises a polypeptide (e.g., any TRX1 or PDI sequence described herein), wherein the polypeptide is present in a pharmaceutical composition at a concentration of 100 pg/mL to 50 µg/mL, or in an amount of 0.5 to 5 µg. In some embodiments, the polypeptide is present in the pharmaceutical composition in a unit dose amount. [0082] In some embodiments, the disclosure provides a method of treating an ocular disease, disorder, or condition in a subject in need thereof, the method comprising administering an effective amount of any TRX enzyme or PDI, or any pharmaceutical composition comprising the same described herein, to at least one cell of the eye, the lacrimal gland and/or the nasolacrimal duct, including without limitation, acinar cells, ductal cells, and/or myoepithelial cells, as well as cells of the iris and ciliary body (“ICB”), lens epithelial cells, cells of a meibomian gland and the trabecular meshwork. [0083] In some embodiments, the disclosure provides a method of treating an ocular disease, disorder, or condition in a subject in need thereof, the method comprising administering an effective amount of a vector encoding any TRX enzyme or PDI, or any pharmaceutical composition comprising the same described herein, to at least one cell of the 037525.00573 eye, the lacrimal gland and/or the nasolacrimal duct, including without limitation, acinar cells, ductal cells, and/or myoepithelial cells, as well as cells of the iris and ciliary body (“ICB”), lens epithelial cells, cells of a meibomian gland and the trabecular meshwork. [0084] In some embodiments, the ocular condition is a) associated with increased oxidative stress; b) associated with loss of expression and/or function of one or more oxidoreductase enzymes; c) associated with loss of TRX expression and/or function; and/or d) associated with loss of PDI expression and/or function. In some embodiments, the ocular condition is characterized by a loss of near vision. In some embodiments, the ocular condition is: a) presbyopia; b) cataract formation; c) ocular hypertension; d) meibomian gland dysfunction (MDI); and/or e) glaucoma. [0085] In some embodiments, the method of treatment results in: a) expression of the oxidoreductase enzyme in the cells of the lacrimal gland and/or the cells of an accessory lacrimal gland, and/or in cells of the trabecular meshwork; b) expression of TRX in the cells of the lacrimal gland and/or cells of an accessory lacrimal gland, and/or in cells of the trabecular meshwork; and/or c) secretion of TRX into the tear film and/or onto the ocular surface of the subject. [0086] In some embodiments, the method of treatment results in a) an improvement of one or more symptoms of the ocular condition; b) an improvement of visual acuity; c) a reduced need for corrective lenses; and/or d) a delay of the progression of the ocular condition. In some embodiments, the method results in the progression of the ocular condition in the subject being delayed by about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to about 80%, about 80% to about 90%, about 90% to about 95% or by more than about 95% compared to a control subject. In some embodiments, the method of treatment results in expression of a functional oxidoreductase enzyme in one or more cells of a lacrimal gland and/or an accessory lacrimal gland of the subject. In some embodiments, the method of treatment results in secretion of a functional oxidoreductase enzyme into a tear film of the subject. In some embodiments, secretion of the functional oxidoreductase enzyme into the tear film is stimulated by a cholinergic agonist. [0087] In some embodiments, the method of treatment results in a reduction of one or more symptoms of an ocular disease, disorder, or condition, e.g., reduced itching, swelling, tearing, and redness. In some embodiments, the administration results in an improvement of 0.5 points, 037525.00573 1 point, 1.5 points, 2 points, 2.5 points, 3 point, 3.5 points, or 4 points on the Conjunctival Itching Grading Scale. [0088] In some embodiments, the disclosure provides a kit comprising any pharmaceutical composition described herein and instructions for use in treating a condition in a human subject, wherein the instructions comprise administering the pharmaceutical composition to an eye of the human subject. [0089] In some embodiments, the disclosure provides a pharmaceutical composition according to any embodiment described herein for use in the manufacture of a medicament for treating a condition in a human subject in need thereof. [0090] In some embodiments, the disclosure provides a pharmaceutical composition according to any of the embodiments described herein for use in a method of treatment according to any of the embodiments described herein. BRIEF DESCRIPTION OF THE FIGURES [0091] FIG.1 shows a vector map of an rAAV expression cassette with inverted terminal repeats (ITRs), a promoter, and TRX polynucleotide elements. [0092] FIGs.2A-2B show examples of delivery of a viral vector to the lacrimal gland of a human subject. [0093] FIG. 3 shows fluorescent microscopy images of 293T cells transfected with AAV.TRX plasmid DNA (bottom row) and stained with an anti-thioredoxin (anti-TRX) primary and counterstained with DAPI. Images show fluorescence emission for anti-TRX at 20X and 40X magnification (respectively middle and right columns) and DAPI (left column). Control 293T cells were non-transfected cells (middle row) or labeled with a secondary control antibody (top row). [0094] FIGs. 4A-4B show bar graphs measuring TRX in supernatant of 293T cells that were untransfected and following 4 days of culture (FIG. 4A) or at 24 hours following transfection with AAV.TRX plasmid (FIG.4B). [0095] FIG. 5 provides an image of a Western Blot to detect TRX in cell lysate obtained from cells that are non-transfected (293T) or transfected (AAV.TRX) 293T cells. Detection of GAPDH was used as a loading control. Whole cell extracts (30 µg/lane) were run on SDS- PAGE and anti-TRX and anti-GAPDH primary antibodies were utilized to detect the respective proteins. 037525.00573 [0096] FIG.6 provides an image of a Western Blot to detect expressed and secreted TRX in cell culture cell media obtained from cells non-transfected (293T) and transfected (AAV.TRX) 293T cells. Protein collected from conditioned cell culture media (30 µg/lane) were run on SDS-PAGE and an anti-TRX and an anti-GAPDH primary antibodies were utilized to detect the respective proteins. [0097] FIG.7 shows a schematic diagram depicting the elements between the ITRs of an AAV plasmid. The plasmid encodes EGFP linked to a secretion signal at its N-terminus (“secEGFP”) under control of a CMV promoter. The woodchuck hepatitis virus post- translational regulatory element (WPRE) serves to increase transgene expression and is proximal to the bovine growth hormone polyadenylation (pA) signal. [0098] FIGs. 8A-8K are images of lacrimal tissue stained with anti-eGFP antibody. Lacrimal glands were dosed with rAAV vectors containing an expression cassette with eGFP transgene by intralacrimal injection. Lacrimal tissue was stained with anti-eGFP antibody to assess eGFP expression. Black arrows indicate staining showing eGFP expression. [0099] FIG. 9 provides images of porcine lacrimal gland that received an injection of AAV-secEGFP (AAV2 or AAV9 serotype) and was harvested on Day 103 and fixed in paraffin. IHC of 5 µM sections was performed using anti-GFP antibody and DAPI (nuclear) counterstain. Images were captured using a confocal microscope at 100X magnification. Negative control animals received no injection. [0100] FIG. 10 provides an image of porcine lacrimal gland that received an injection of AAV9-secEGFP and was harvested on Day 103 and fixed in paraffin. IHC of 5 µM sections was performed using anti-GFP antibody and DAPI (nuclear) counterstain. In addition to lacrimal gland acinar cells, ductile epithelial cells appear to be transduced by AAV9 (white arrows). [0101] FIG. 11 provides an image of porcine lacrimal gland that received an injection of AAV was harvested at Day 103 and fixed in paraffin. H&E staining of 5µM paraffin sections at 100x reveal no inflammatory infiltrate, macro, or micro abnormalities. [0102] FIG. 12 provides a schematic of a treatment schedule for administering AAV encoding a model protein via injection into the lacrimal gland of pigs in combination with administration of OC-01 (Varenicline) by nasal spray. Time points for tear collection and termination of the study are indicated. 037525.00573 [0103] FIG. 13 shows the results of a Western Blot analysis conducted with an anti- thioredoxin primary antibody (ThermoFisher Catalog #14999-1-AP) and an anti-rabbit IgG HRP secondary antibody (ProMega Catalog #A5316). [0104] FIG.14 provides an image of a Western Blot to detect TRX in cell lysate obtained from cells that are non-transfected (293T) or transfected (AAV.TRX) 293T cells. Detection of actin was used as a loading control. Whole cell extracts (30 µg/lane) were run on SDS-PAGE and anti-TRX and anti-actin primary antibodies were utilized to detect the respective proteins. [0105] FIG. 15 is a graph showing the results of a TRX activity assay. The 293T cells transfected with the thioredoxin transgene plasmid exhibited thioredoxin activity of 56.8 nm/minute and the non-transfected 293T cells demonstrated an endogenous thioredoxin activity level of 16.90 nM/minute. This functional assay confirmed the expression, secretion and function of the transgene product from the construct depicted in FIG.1. DETAILED DESCRIPTION [0106] The present disclosure provides methods of treating an ocular condition in a subject in need thereof. Such methods comprise, e.g., the expression of an oxidoreductase enzyme (such as TRX and/or PDI) in the eye. As disclosed herein, AAV-based delivery of transgenes to the eye provides a method to treat ocular disorders. rAAV vectors have distinct advantages for transgene delivery. A transgene delivered by an rAAV vector will not likely be incorporated into the genome of the transduced cell to support chronic expression and genomic passage of the transgene product. rAAV vectors transport the transgene of interest through the cellular membrane and into the nucleus of target cells where the transgene does not integrate into the genome for transcription, but rather in episomal form. Given the episomal nature of the transgene, the expression of the transgene delivered is dependent upon cellular turnover in any given tissue of transduced cells (BioDrugs.2017; 31(4): 317–334). The advantage is relatively controlled expression duration without genomic passage of the transgene, especially into germ cells. In addition, rAAV vectors (e.g., rAAV virions described herein), are not as immunogenic as other viral delivery vectors, such as adenovirus. AAV-based delivery vectors using subretinal and intravitreal injection to transduce cells in the posterior segment of the eye are described and show efficacy in vivo (U.S. Pat. No. 10,308,957; Petrs-Silva et al., Mol Ther.19:293-301 (2011); Rodriques et al., Pharm Res.36:29 (2019)). [0107] AAV serotypes used in AAV-based delivery of transgene to the eye include AAV1, AAV2, AAV4, AAV5, AAV6, AAV7, AAV8, and AAV9 used to deliver transgene (Lebherz 037525.00573 et al. J Gene Med.; 10(4): 375–382 (2008)). AAV serotypes used in AAV-based delivery of a transgene to the lacrimal gland include AAV2, AAV4, AAV5, AAV5w8, AAV x5, AAV 9, AAV 12, and BAAV (Rocha et al., Invest Ophthalmol Vis Sci.52:9567–9572 (2011)). [0108] In some embodiments, the disclosure provides an rAAV vector for the expression of a polypeptide of the thioredoxin superfamily. In some embodiments, the polypeptide is TRX. In some embodiments, the polypeptide is PDI. In some embodiments, the disclosure provides an rAAV vector for the expression of TRX (e.g., human TRX). In some embodiments, the disclosure provides an rAAV vector for expression of PDI (e.g., human PDI). [0109] In some embodiments, cells of at least one eye and/or lacrimal gland are transduced with the rAAV vector of the disclosure. The lacrimal glands are the major source of tear fluid responsible for promoting a healthy ocular surface and maintaining normal visual function. The main lacrimal gland comprises palpebral and orbital lobes, which are continuous with each other at the lateral edge of the aponeurosis of levator palpebrae superioris. The lobules have many acini and intralobular ducts that form excretory ducts that open into the fornix of the conjunctiva. The main lacrimal gland is comprised of acinar cells, ductal cells, and/or myoepithelial cells (Obata Cornea.; 25(10 Suppl 1):S82-9 (2006)). The main lacrimal gland secretes an aqueous layer of tear film as well as mucins onto the ocular surface of the eye of a subject (see, e.g., Paulsen, F., et al (2004) Cell and tissue research, 316(2), 167-177). As used herein, the term “lacrimal gland” refers to the main lacrimal gland, as well as the Wolfring’s glands and the Krause’s glands of a subject. The accessory glands, known as the Wolfring’s glands and Krause’s glands are located in the eyelid. In the upper eyelid there are about 2 to 5 Wolfring’s glands and about forty Krause’s glands. In the lower eyelid there are about 6 to 8 Krause’s glands. Specific location and anatomy of the lacrimal functional unit is well-known (Conrady et al., J Ophthalmol. Article ID 7542929 (2016)). [0110] Oxidative stress associated with aging is known to alter the structure and function of the lacrimal gland and lead to acinar atrophy and fibrosis. (Rocha, E et. al., Ocul Surf.2008 Oct.; 6(4)). Without being bound by theory, alteration of proteins in the lacrimal gland, e.g., as a result of oxidation and resultant disulfide bond formation, decreases the neural stimulation (efferent parasympathetic and sympathetic) and protein secretion function of the lacrimal gland, thereby reducing tear output with respect to quantity and quality. It is thought that this decreased function of the lacrimal gland contributes to dry eye disease. Moreover, a similar mechanism occurs in another region of the lacrimal functional unit, the meibomian glands. Meibomian glands are mostly responsible for the production of the lipid layer of the tear film 037525.00573 and loss of function results in meibomian gland dysfunction (MGD). The loss or drop-out of meibomian glands due to atrophy can be directly correlated with MGD (Chhadya, P. et.al., Ophthalmology.2017 Nov; 124(11)) and ductual occlusion/obstruction due to fibrosis can lead to atrophy and loss of function, further contributing to ocular surface disease. [0111] The trabecular meshwork is an ocular drainage network located in the iridocorneal angle (where the iris and cornea meet and the sclera transitions into the cornea). The trabecular meshwork is a small, porous triangle (approximately 350 × 50–150 μm in cross section) composed of connective tissue beams and sheets or lamellae covered by trabecular meshwork cells (Abu-Hassan et al., J Ocul Biol.2014 May;2(1)). Trabecular mesh cells play an important role in the maintenance of intraocular pressure by adjusting the outflow resistance of the aqueous humor. Oxidative stress alters the structure of the trabecular meshwork by which outflow resistance is increased and ultimately leads to increased intraocular pressure (IOP) and damage to the optic nerve (International Journal of Medicine Oct 2016; Vol 38 Issue 4; 995- 1002). This damage can further lease to increased and progressive visual field loss. Without being bound by theory, increased expression of TRX and/or PDI in the trabecular meshwork serves to reverse and/or prevent additional disulfide bond formation, thereby decreasing outflow resistance and associated optic nerve damage. [0112] The retina is a light-sensitive layer of nerve tissue at the back of the eye that receives light impulses, sends them as electric signals through the optic nerve to the brain for visual recognition. Retinal photoreceptors and retinal ganglion cell survival requires an equilibrium between oxygen, reactive oxygen species, and antioxidant molecules that counteract oxidative stress. Oxidative stress can alter cell homeostasis, thus eliciting a protective response, especially in cells such as photoreceptors and retinal ganglion cells that have a high metabolic rate that are continuously subject to light/oxidative stress insults (B. Domènech, E., & Marfany, G. (2020). Oxidative stress is thought to contribute to the pathogenesis and therapy of retinal dystrophies. See, e.g., Antioxidants, 9(4), 347.). Thioredoxin Enzyme [0113] In some embodiments, the expression cassette of the present disclosure comprises a polynucleotide sequence encoding a Thioredoxin (TRX) enzyme or a functional variant thereof. The TRX enzyme has a dithiol Cys-Gly-Pro-Cys (CGPC) active site motif that is highly conserved among all kingdoms of life (Holmgren A. J Biochem. (1968) 6:475–484). In mammals, there are at least two enzymes capable of reducing oxidized cysteines in proteins 037525.00573 through a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reaction, including TRX1 and TRX2 (Lee, et al (2013) Antioxid Redox Signal 18:1165-1207). TRX1 is typically localized to the cytosol, and is translocated to the nucleus or secreted. TRX2 is typically localized to the mitochondria. [0114] As used herein, the term “Thioredoxin”, “TRX”, or “TRX enzyme” refers to a TRX1 protein from any species. In some embodiments, TRX1 protein is human. The term “functional variant” refers to variants having sequence substitutions, insertions, deletions, and/or N- or C-terminal truncations, where the functional variant retains one or more functions of the reference protein, e.g., a native TRX enzyme. Thioredoxin is a protein that forms a homodimer and functions as an oxidoreductase. [0115] In some embodiments, the TRX enzyme is a human TRX enzyme. In some embodiments, the human TRX enzyme is identified in a public database. Human TRX isoforms known in the art are typically identified via public databases. For example, the National Library of Medicine National Center for Biotechnology Information (NCBI) Gene Database (accessible via the world wide web: ncbi.nlm.nih.gov/) is a searchable database of genes that provides nomenclature, chromosomal localization, gene products, attributes of the gene, associated markers, phenotypes, interactions, links to citations, sequence information, information regarding sequence variants, gene maps, expression reports, homologs, protein domain content, and access to external databases. As is understood by the skilled artisan, sequence information for human TRX isoforms known in the art may be identified by entering the appropriate accession number into the NCBI Gene Database and selecting sequence information in the desired computer-readable format (e.g., FASTA). Such sequence information may include, but is not limited to, the nucleotide sequence for the full-length gene encoding TRX, the nucleotide sequence of the pre-mRNA transcript encoding TRX, the nucleotide sequence of the mRNA encoding TRX, the nucleotide sequence of the open reading frame (ORF) encoding TRX, and the amino acid sequence of TRX. For example, one isoform of human TRX is identifiable in the NCBI gene database via the Gene ID number 7295 and has the amino acid sequence set forth in SEQ ID NO: 25. [0116] Exemplary amino acid sequences of human TRX and exemplary polynucleotide sequences (mRNA and ORF) encoding human TRX are set forth in [0117] Table . In some embodiments, the TRX enzyme comprises or consists of an amino acid sequence set forth in Table 1. In some embodiments, the TRX enzyme comprises or consists of an amino acid sequence encoded by an mRNA sequence set forth in Table 1. In 037525.00573 some embodiments, the TRX enzyme comprises or consists of an amino acid sequence encoded by an ORF set forth in Table 1. [0118] In some embodiments, the TRX enzyme comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 1. In some embodiments, the TRX enzyme comprises or consists of SEQ ID NO: 1. In some embodiments, the TRX enzyme comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 25. In some embodiments, the TRX enzyme comprises or consists of SEQ ID NO: 25. [0119] In some embodiments, the TRX enzyme is encoded by an ORF comprising or consisting of a nucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 2. In some embodiments, the TRX enzyme is encoded by an ORF comprising or consisting of SEQ ID NO: 2. [0120] In some embodiments, the TRX enzyme is encoded by an ORF comprising or consisting of a nucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 28. In some embodiments, the TRX enzyme is encoded by an ORF comprising or consisting of SEQ ID NO: 28. [0121] In some embodiments, the TRX enzyme is a truncated version of any of the TRX enzyme sequences described herein (e.g., SEQ ID NOs: 1 or 25). For example, in some embodiments the TRX enzyme is a fragment comprising at least 20, 40, 60, 80, or 100 contiguous amino acids of SEQ ID NOs: 1 or 25. In some embodiments the TRX enzyme is a fragment comprising at least 20, 40, 60, 80, or 100 contiguous amino acids of SEQ ID NOs: 1 or 25, wherein the fragment has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid substitutions, insertions or deletions as compared to SEQ ID NOs: 1 or 25. In some embodiments the TRX enzyme is a fragment comprising at least 10, 20, 3040, 50, 60, 70, 80, 90, or 100 contiguous amino acids of SEQ ID NOs: 1 or 25, or a fragment having a length within a range with endpoints selected from any pair of the foregoing lengths. Any of the truncated versions of the TRX enzyme sequences described herein (e.g., SEQ ID NOs: 1 or 25) may include one or more amino acid substitutions, insertions, or deletions, and may share at least 85, 90, 95, 96, 97, 98, 99, or 100% sequence identity with SEQ ID NOs: 1 or 25. 037525.00573 Polynucleotides Encoding a TRX Enzyme [0122] In some embodiments, the expression cassette comprises a polynucleotide encoding a TRX enzyme described herein (e.g., a human TRX enzyme). In some embodiments, the polynucleotide comprises an ORF encoding a TRX enzyme described herein (e.g., a human TRX enzyme). [0123] In some embodiments, the expression cassette provides increased expression of TRX in at least one eye, and/or lacrimal gland. In some embodiments, the expression cassette provides increased expression of TRX in at least one meibomian gland. In some embodiments, the expression cassette provides increased expression of TRX in the trabecular meshwork. In some embodiments, the expression cassette provides increased expression of TRX in the retina. In some embodiments, expression of TRX is increased 5%, 10%, 15%, 20%, or 25% compared to expression of TRX in an untreated subject, or in the contralateral eye of a treated subject. As used herein, “subject” means any mammal, including mice, rabbits, non-human primates (NHP) and humans. In some embodiments, the subject is a human or NHP. Moreover, “individual” or “patient” may be used interchangeably with “subject.” In some embodiments, expression of TRX is increased by at least 1.5-fold, 2-fold, 3-fold, 4-fold, or 5-fold compared to expression of TRX in an untreated subject, or in the contralateral eye of a treated subject. In some embodiments, TRX expression is at any detectable level in the treated eye, whereas TRX may not be expressed, or expressed at undetectable levels, in an untreated subject, or in the contralateral eye of a treated subject. Put another way, the eye or lacrimal gland to which an rAAV vector described herein is administered may express TRX in higher abundance than in an eye or lacrimal gland that has only endogenous (i.e., native) expression of TRX or in eyes that have a lower or impaired secretion of endogenous (i.e., native) TRX. [0124] The term “functional variant” refers to variants having sequence substitutions, insertions, deletions, and/or N- or C-terminal truncations, where the functional variant retains one or more functions of the reference protein, e.g., native TRX. [0125] In some embodiments, the expression cassette comprises a polynucleotide encoding a protein that is human TRX or a functional variant thereof. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding an amino acid sequence identified in Table 1. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence identified in Table 1. 037525.00573 [0126] In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding a protein having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding a protein having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to the amino acid sequence set forth in SEQ ID NO: 25. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 25. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 2. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence set forth in SEQ ID NO: 2. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 28. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence set forth in SEQ ID NO: 28. [0127] In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises or consists of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 1. In some embodiments, the TRX enzyme comprises or consists of SEQ ID NO: 1. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises or consists of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 25. In some embodiments, the TRX enzyme comprises or consists of SEQ ID NO: 25. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises or consists of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, 037525.00573 at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 24. In some embodiments, the TRX enzyme comprises or consists of SEQ ID NO: 24. [0128] Percent identity can be determined using any suitable method known in the art. For example, a method of determining percent identity of a nucleic acid sequence is genome sequencing. Methods for determining percent identity to a nucleic acid sequence or amino acid sequence are known to those of skill in the art. Protein Disulfide Isomerase [0129] In some embodiments, the expression cassette of the present disclosure comprises a polynucleotide sequence encoding a Protein Disulfide Isomerase (PDI) or a functional variant thereof. The ability of PDI to reduce disulfide bonds is a critical protection against oxidative stress and diseases associated with disulfide bond formation in an oxidative environment due to normal aging, disease, environmental or pharmacological events such as the case with cataract formation and presbyopia, but also potentially involved in dry eye disease, meibomian gland dysfunction and ocular hypertension/glaucoma. PDI also contains a thioredoxin active site with a CXXC motif further supporting a potential role for PDI in disulfide bond reduction to reduce disease states in various tissues. Protein disulfide isomerase (Gene name: P4HB) is a 508 amino acid protein with a mass of approximately 57.1 kilodaltons (also referred to as ERBA2L, PDI, PDIA1, PO4DB). [0130] As used herein, the term “protein disulfide isomerase” or “PDI” refers to a PDI protein for any species. The term “functional variant” refers to variants having sequence substitutions, insertions, deletions, and/or N- or C-terminal truncations, where the functional variant retains one or more functions of the reference protein, e.g., a native PDI. [0131] In some embodiments, the PDI is a human PDI enzyme. In some embodiments, the human PDI is identified in a public database. Human PDI isoforms known in the art are typically identified via public databases. As is understood by the skilled artisan, sequence information for human PDI isoforms known in the art may be identified by entering the appropriate accession number into the NCBI Gene Database and selecting sequence information in the desired computer-readable format (e.g., FASTA). Such sequence information may include, but is not limited to, the nucleotide sequence for the full-length gene encoding TRX, the nucleotide sequence of the pre-mRNA transcript encoding PDI, the nucleotide sequence of the mRNA encoding PDI, the nucleotide sequence of the open reading frame (ORF) encoding PDI, and the amino acid sequence of PDI. For example, one isoform of 037525.00573 human PDI is identifiable in the NCBI gene database via the Gene ID number 5034 and has the amino acid sequence set forth in SEQ ID NO: 26. [0132] Exemplary amino acid sequences of human PDI and exemplary polynucleotide sequences (mRNA and ORF) encoding human PDI are set forth in Table 2. In some embodiments, the PDI comprises or consists of an amino acid sequence set forth in Table 2. In some embodiments, the PDI comprises or consists of an amino acid sequence encoded by an mRNA sequence set forth in Table 2. In some embodiments, the PDI comprises or consists of an amino acid sequence encoded by a nucleic acid sequence set forth in Table 2. [0133] In some embodiments, the PDI comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to the sequence spanning positions 24-474 of SEQ ID NO: 26. In some embodiments, the nucleic acid encoding PDI comprises or consists of SEQ ID NO: 30. [0134] In some embodiments, the PDI is a truncated version of any of the PDI sequences described herein (e.g., SEQ ID NO: 26). For example, in some embodiments the PDI is a fragment comprising at least a 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, or 500 contiguous amino acids of SEQ ID NO: 26. In some embodiments the PDI is a fragment comprising at least a 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, or 500 contiguous amino acids of SEQ ID NO: 26, wherein the fragment has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acid substitutions, insertions or deletions as compared to SEQ ID NO: 26. In some embodiments the PDI is a fragment comprising at least 10, 20, 3040, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, or 500 contiguous amino acids of SEQ ID NO: 26, or a fragment having a length within a range with endpoints selected from any pair of the foregoing lengths. Any of the truncated versions of the PDI sequences described herein (e.g., SEQ ID NOs: 26) may include one or more amino acid substitutions, insertions, or deletions, and may share at least 85, 90, 95, 96, 97, 98, 99, or 100% sequence identity with SEQ ID NO: 26, or with the sequence spanning positions 24-474 of SEQ ID NO: 26. 037525.00573 Polynucleotides Encoding PDI [0135] In some embodiments, the expression cassette comprises a polynucleotide encoding a PDI enzyme described herein (e.g., a human PDI enzyme). In some embodiments, the polynucleotide comprises an ORF encoding a PDI enzyme described herein (e.g., a human PDI enzyme). [0136] In some embodiments, the expression cassette provides increased expression of PDI in at least one eye and/or lacrimal gland. In some embodiments, the expression cassette provides increased expression of PDI in at least one meibomian gland. In some embodiments, the expression cassette provides increased expression of PDI in the trabecular meshwork. In some embodiments, expression of PDI may be increased 5%, 10%, 15%, 20%, or 25% compared to expression of PDI in an untreated subject, or in the contralateral eye of a treated subject. In some embodiments, expression of PDI may be increased by at least 1.5-fold, 2-fold, 3-fold, 4-fold, or 5-fold compared to expression of TRX in an untreated subject, or in the contralateral eye of a treated subject. In some embodiments, PDI may be expression at any detectable level in the treated eye, whereas PDI may not be expressed, or expressed at undetectable levels, in an untreated subject, or in the contralateral eye of a treated subject. Put another way, the eye or lacrimal gland to which an rAAV vector described herein is administered may express PDI in higher abundance than in an eye or lacrimal gland that has only endogenous (i.e., native) expression of PDI or in eyes that have a lower or impaired secretion of endogenous (i.e., native) PDI. [0137] The term “functional variant” refers to variants having sequence substitutions, insertions, deletions, and/or N- or C-terminal truncations, where the functional variant retains one or more functions of the reference protein, e.g., native PDI. [0138] In some embodiments, the expression cassette comprises a polynucleotide encoding a protein that is human PDI or a functional variant thereof. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding an amino acid sequence identified in Table 2. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence identified in Table 2. [0139] In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding a protein having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the expression cassette 037525.00573 comprises a polynucleotide comprising a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 30. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence set forth in SEQ ID NO: 30. [0140] In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding a PDI, wherein the PDI comprises or consists of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises or consists of SEQ ID NO: 26. In some embodiments, the expression cassette comprises a polynucleotide comprising a nucleotide sequence encoding a PDI, wherein the PDI comprises or consists of an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises or consists of SEQ ID NO: 26. Codon Optimization [0141] In some embodiments, the expression cassette comprises a polynucleotide encoding a TRX enzyme or PDI enzyme, wherein the polynucleotide comprises or consists of a nucleotide sequence codon-optimized for expression in a target cell. In some embodiments, the target cell is a mammalian cell. In some embodiments, the target cell is a human cell, a murine cell, or a non-human primate (NHP) cell. [0142] A codon-optimized nucleotide sequence, e.g., a codon-optimized nucleotide sequence encoding a TRX enzyme or PDI, typically is a sequence comprising at least one synonymous nucleobase substitution with respect to a reference sequence (e.g., a wild-type ORF encoding a TRX enzyme or a wild-type ORF encoding a PDI). A codon-optimized nucleotide sequence can be partially or completely different in sequence from the reference sequence. For example, a reference sequence encoding polyserine uniformly encoded by TCT codons can be sequence-optimized by having 100% of its nucleobases substituted (for each codon, T in position 1 replaced by A, C in position 2 replaced by G, and T in position 3 replaced by C) to yield a sequence encoding polyserine which would be uniformly encoded by AGC codons. The percentage of sequence identity obtained from a global pairwise alignment 037525.00573 between the reference polyserine nucleic acid sequence and the sequence-optimized polyserine nucleic acid sequence would be 0%. However, the protein products from both sequences would be 100% identical. [0143] Codon optimization methods are known in the art and can be useful to achieve one or more desired results, e.g., to increase expression of a synthetic gene in a target cell. In some embodiments, an expression cassette comprises a nucleotide sequence that is sequence- optimized relative to a reference sequence using a method of sequence optimization. Methods of sequence optimization are known in the art, and include known sequence optimization tools, algorithms and services. Non-limiting examples include services from GeneArt (Life Technologies), DNA2.0 (Menlo Park CA), Geneious®, and GeneGPS® (Atum, Newark, CA). [0144] In some embodiments, an expression cassette of the disclosure comprises a polynucleotide encoding a TRX enzyme or a PDI enzyme that is sequence-optimized relative to a reference sequence using a method of sequence optimization (e.g., GeneGPS®, e.g., Geneious®). In some embodiments, the reference sequence encoding TRX is set forth in SEQ ID NO: 28. In some embodiments, the expression cassette comprises a polynucleotide encoding TRX that is a sequence optimized relative to the reference sequence encoding TRX. In some embodiments, the reference sequence encoding TRX is set forth in SEQ ID NO: 28 and the codon-optimized sequence encoding TRX is set forth in SEQ ID NO: 2. In some embodiments, the reference sequence encoding PDI is set forth in SEQ ID NO: 30. In some embodiments, the expression cassette comprises a polynucleotide that is a sequence optimized relative to the reference sequence encoding PDI. [0145] In some embodiments, the method of sequence optimization comprises a codon optimization algorithm described in US 7,561,972; US 7,561,973; US 8,126,653; and US 8,401,798, each of which is incorporated herein by reference. In some embodiments, the polynucleotide sequence is sequence-optimized based on codon usage bias in a host cell (e.g., mammalian cell, e.g., human cell, murine cell, non-human primate cell) relative to a reference sequence, using a method of sequence optimization known in the art (e.g., GeneGPS®, e.g., Geneious®). In some embodiments, the polynucleotide sequence comprises or consists of a nucleotide sequence that is codon-optimized relative to a reference sequence using a method of sequence optimization. In some embodiments, the polynucleotide sequence comprises or consists of a nucleotide sequence that is codon-optimized relative to a reference sequence for expression in a human host cell. In some embodiments, the polynucleotide sequence comprises or consists of SEQ ID NO: 2. 037525.00573 [0146] In some embodiments, the disclosure provides an expression cassette comprising a polynucleotide comprising or consisting of a nucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 2. In some embodiments, the polynucleotide comprises or consists of SEQ ID NO: 2. Table 1: Human TRX Amino Acid and Polynucleotide Sequences Table 2: Human PDI Amino Acid and Polynucleotide Sequences Expression Cassettes [0147] The vectors of the disclosure comprise an expression cassette. As used herein, the term “expression cassette” refers to a polynucleotide comprising at least one polynucleotide sequence encoding a protein of interest (e.g., TRX or PDI). In some embodiments, (e.g., where the vector is an rAAV virion), the expression cassette may further comprise inverted terminal repeats flanking both sides of the at least one polynucleotide sequence encoding a protein of interest. In some embodiments, the protein of interest is a member of the thioredoxin superfamily. In some embodiments, the protein of interest is an oxidoreductase enzyme. In some embodiments, the protein of interest is TRX. In some embodiments, the protein of interest is protein disulfide isomerase (PDI). In some embodiments, the expression cassette comprises other polynucleotide sequences, e.g., promoters, regulatory elements (e.g., one or more promoters), translation initiation sequences, coding sequences, and termination sequences. [0148] In some embodiments, the expression cassette of the present disclosure comprises a polynucleotide sequence encoding an oxidoreductase enzyme (e.g., TRX or PDI) or a functional variant thereof. In some embodiments, the expression cassette provides increased expression of TRX in at least one eye, the lacrimal gland, and/or the trabecular meshwork. In some embodiments, expression of TRX may be increased 5%, 10%, 15%, 20%, or 25% compared to expression of TRX in an untreated subject, or in the contralateral eye of a treated subject. In some embodiments, expression of TRX may be increased 1.3-fold, 1.5-fold, 1.7- 037525.00573 fold, 1.9-fold, 2-fold, 3-fold, 4-fold, or 5-fold compared to expression of TRX in an untreated subject, or in the contralateral eye of a treated subject. In some embodiments, TRX may be expression at any detectable level in the treated eye, whereas TRX may not be expressed, or expressed at undetectable levels, in an untreated subject, or in the contralateral eye of a treated subject. Put another way, the eye, the lacrimal gland, the meibomian glands, and/or the trabecular meshwork to which an rAAV vector described herein is administered may express the oxidoreductase enzyme (e.g., TRX or PDI) in higher abundance than in an eye, lacrimal gland, meibomian gland, and/or trabecular meshwork that has only endogenous (i.e., native) expression of the oxidoreductase enzyme (e.g., TRX or PDI) or in eyes that have a lower or impaired secretion of endogenous (i.e., native) forms of the oxidoreductase enzyme (e.g., TRX or PDI). [0149] The term “functional variant” refers to variants having sequence substitutions, insertions, deletions, and/or N- or C-terminal truncations, where the functional variant retains one or more functions of the reference protein, e.g., native TRX. [0150] In some embodiments, provided herein are expression cassettes comprising a polynucleotide encoding TRX. Exemplary amino acid sequences of TRX and exemplary polynucleotide sequences encoding TRX are set forth in Table 3. Table 3: TRX Amino Acid and Polynucleotide Sequences [0151] In some embodiments, the polynucleotide encodes a protein which shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 1. In some embodiments, the polynucleotide encodes a protein which shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 25. In some embodiments, the polynucleotide encodes a protein that is human TRX or a functional variant thereof. 037525.00573 [0152] In some embodiments, the polynucleotide encoding TRX comprises a sequence that shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 2. In some embodiments, the polynucleotide encoding TRX comprises a sequence that shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 28. In some embodiments, the protein is human TRX or a functional variant thereof. [0153] In some embodiments, the polynucleotide encoding TRX also encodes a signal peptide. A signal peptide facilitates the expression and subcellular localization of a protein. In some embodiments, the signal peptide shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 3. In some embodiment, the polynucleotide comprises a sequence that shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 4. [0154] In some embodiments, an expression cassette provided herein comprises a transgene encoding an oxidoreductase enzyme that is not TRX. [0155] In some embodiments, an expression cassette provided herein is a bicistronic expression cassette configured to allow the simultaneous expression of two proteins using a single mRNA transcript (e.g., via the incorporation of an internal ribosomal entry site, “IRES”). For example, a bicistronic expression cassette may comprise both a TRX enzyme sequence and a PDI sequence selected from any of the sequences or embodiments described herein. In some embodiments, co-expression of TRX and PDI in a cell of the eye may provide synergistic therapeutic effects. [0156] In some embodiments, the expression cassette provides increased expression of PDI in at least one eye, the lacrimal gland, at least one meibomian gland, and/or the trabecular meshwork. In some embodiments, expression of PDI may be increased 5%, 10%, 15%, 20%, or 25% compared to expression of PDI in an untreated subject, or in the contralateral eye of a treated subject. In some embodiments, expression of PDI may be increased 1.3-fold, 1.5-fold, 1.7-fold, 1.9-fold, 2-fold, 3-fold, 4-fold, or 5-fold compared to expression of PDI in an untreated subject, or in the contralateral eye of a treated subject. In some embodiments, PDI may be expressed at any detectable level in the treated eye, whereas PDI may not be expressed, or expressed at undetectable levels, in an untreated subject, or in the contralateral eye of a treated subject. Put another way, the eye, the lacrimal gland, the meibomian glands, and/or the 037525.00573 trabecular meshwork to which an rAAV vector described herein is administered may express the oxidoreductase enzyme (e.g., PDI) in higher abundance than in an eye, lacrimal gland, the meibomian glands, retina, and/or trabecular meshwork that has only endogenous (i.e., native) expression of the oxidoreductase enzyme (e.g., PDI) or in eyes that have a lower or impaired secretion of endogenous (i.e., native) forms of the oxidoreductase enzyme (e.g., PDI). [0157] The term “functional variant” refers to variants having sequence substitutions, insertions, deletions, and/or N- or C-terminal truncations, where the functional variant retains one or more functions of the reference protein, e.g., native PDI. [0158] In some embodiments, the polynucleotide encodes a protein which shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 26. In some embodiments, the polynucleotide encodes a protein that is human PDI or a functional variant thereof. [0159] In some embodiments, the polynucleotide encoding PDI comprises a sequence that shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 30. In some embodiments, the protein is human PDI or a functional variant thereof. [0160] In some embodiments, the polynucleotide encoding PDI also encodes a signal peptide. A signal peptide facilitates the expression and subcellular localization of a protein. In some embodiments, the signal peptide shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 3. In some embodiment, the polynucleotide comprises a sequence that shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 4. [0161] In some embodiments, the expression cassette of the present disclosure comprises a promoter. The term “promoter” as used herein refers to a DNA sequence that directs the binding of RNA polymerase and thereby promotes RNA synthesis, i.e., a minimal sequence sufficient to direct transcription. Promoters and corresponding protein or polypeptide expression may be ubiquitous, meaning strongly active in a wide range of cells, tissues and species or cell-type specific, tissue-specific, or species specific. Promoters may be “constitutive,” meaning continually active, or “inducible,” meaning the promoter can be activated or deactivated by the presence or absence of biotic or abiotic factors. Also included in the nucleic acid constructs or vectors of the disclosure are enhancer sequences that may or 037525.00573 may not be contiguous with the promoter sequence. Enhancer sequences influence promoter- dependent gene expression and may be located in the 5ʹ or 3ʹ regions of the native gene. [0162] Any suitable promoter region or promoter sequence therein can be used in the subject polynucleotide cassettes, so long as the promoter region promotes expression of a polynucleotide sequence encoding an oxidoreductase enzyme (e.g., TRX or PDI) in at least one eye, the lacrimal gland, at least one meibomian gland, and/or the trabecular meshwork. In some embodiments, the promoter promotes expression of the gene in the mammalian eye, the lacrimal gland, the meibomian glands, and/or the trabecular meshwork. In some embodiments, the expression cassette comprises a cell-type specific promoter. The promoter may specifically promote transcription in the cells of the eye, the cells of the lacrimal gland, the cells of a meibomian gland, or the cells of the trabecular meshwork. For example, in some embodiments the promoter may comprise: a corneal stroma specific promoter such as a Keratocan promoter (Carlson EC, et. al., “In Vivo Gene Delivery and Visualization of Corneal Stromal Cells Using an Adenoviral Vector and Keratocyte-Specific Promoter.” Investigative Ophthalmology & Visual Science July 2004, Vol. 45, 2194-2200); a corneal epithelial/limbal stem cell specific promoter, such as a Keratin-12 or Pax-6 promoter (Wang, I., et al. “Cis-regulatory elements of the mouse Krt1.12 gene.” Molecular vision, 8, 94-101 (2002); Yoshihara, M., et al. “High- resolution promoter map of human limbal epithelial cells cultured with keratinocyte growth factor and rho kinase inhibitor.” Sci Rep 7, 2845 (2017); a Trabecular meshwork cell specific promoter such as a Chitinase 3-Like 1 Promoter (Liton PB, et al., “Specific targeting of gene expression to a subset of human trabecular meshwork cells using the chitinase 3-like 1 promoter.” Invest Ophthalmol Vis Sci.2005 Jan;46(1):183-90); or an iris cell specific promoter such as a Phosphodiesterase 11A promoter (Janssen SF, et al., “Gene expression and functional annotation of the human ciliary body epithelia.” PLoS One.2012;7(9):e44973). [0163] In some embodiments, the promoter is a CAG promoter. In some embodiments, the promoter comprises a nucleotide sequence having at least 90%, 95%, 96%, 97%, 98%, or 99% identity with the nucleotide sequence set forth in SEQ ID NO: 5. In some embodiments, the promoter comprises SEQ ID NO: 5. [0164] In some embodiments, the promoter is a CMV promoter. In some embodiments, the promoter comprises a nucleotide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 17. In some embodiments, the promoter comprises or consists of SEQ ID NO: 17. 037525.00573 [0165] In some embodiments, the enhancer is a CMV enhancer. In some embodiments, CMV enhancer comprises a nucleotide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 18. In some embodiments, the promoter comprises or consists of SEQ ID NO: 18. [0166] In some embodiments, the expression cassette comprises a promoter and enhancer. In some embodiments, CMV enhancer and promoter comprises a nucleotide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 19. In some embodiments, the enhancer and promoter comprises or consists of SEQ ID NO: 19. [0167] The expression cassette may contain a polyadenylation (polyA) sequence. In some embodiments, the expression cassettes described herein comprise a transcription termination signal. Elements directing the efficient termination and polyadenylation of the heterologous nucleic acid transcripts increases heterologous gene expression. Transcription termination signals are generally found downstream of the polyadenylation signal. In some embodiments, vectors comprise a polyadenylation sequence 3′ of a polynucleotide encoding a polypeptide to be expressed. The term “polyA site” or “polyA sequence” as used herein denotes a DNA sequence which directs both the termination and polyadenylation of the nascent RNA transcript by RNA polymerase II. Polyadenylation sequences can promote mRNA stability by addition of a polyA tail to the 3′ end of the coding sequence and thus, contribute to increased translational efficiency. Cleavage and polyadenylation is directed by a poly(A) sequence in the RNA. The core poly(A) sequence for mammalian pre-mRNAs has two recognition elements flanking a cleavage-polyadenylation site. Typically, an almost invariant AAUAAA hexamer lies 20-50 nucleotides upstream of a more variable element rich in U or GU residues. Cleavage of the nascent transcript occurs between these two elements and is coupled to the addition of up to 250 adenosines to the 5’ cleavage product. In particular embodiments, the core poly(A) sequence is an ideal polyA sequence (e.g., AATAAA, ATTAAA, AGTAAA). In particular embodiments, the poly(A) sequence is an SV40 polyA sequence, a bovine growth hormone polyA sequence (BGH polyA), a rabbit β-globin polyA sequence (rβgpA), variants thereof, or another suitable heterologous or endogenous polyA sequence known in the art. In some embodiments, the expression cassette described herein comprises a polyA sequence. In some embodiments, the polyA sequence is a BGH polyA sequence. In some embodiments, the BGH polyA sequence comprises or consists of a nucleotide sequence having at least 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 20. In some embodiments, the BGH polyA sequence comprises or consists of SEQ ID NO: 20. 037525.00573 [0168] In some embodiments, the rAAV vectors of the disclosure comprise the Woodchuck Post-transcriptional Regulatory Element (WPRE). In some embodiments, the rAAV vector comprises a WPRE comprising SEQ ID NO: 21. Recombinant AAV Vectors [0169] In some embodiments, the subject expression cassettes are used to deliver an oxidoreductase enzyme (e.g., TRX or PDI) or a functional variant thereof to at least one eye and/or lacrimal gland of a subject, e.g., to treat an ocular disorder. In some embodiments, the subject expression cassettes are used to deliver an oxidoreductase enzyme (e.g., TRX or PDI) or a functional variant thereof to at least meibomian glands of a subject, e.g., to treat an ocular disorder. Accordingly, in some embodiments, the composition that provides for the expression of an oxidoreductase enzyme (e.g., TRX or PDI) or a functional variant thereof in at least one eye and/or lacrimal gland of a subject is a gene delivery vector, wherein the gene delivery vector comprises an expression cassette described herein. [0170] In some embodiments, the gene delivery vector is an rAAV vector (e.g., an rAAV virion). In some embodiments, the expression cassette is flanked on the 5’ and 3’ ends by functional AAV inverted terminal repeat (ITR) sequences. By “functional AAV ITR sequences” is meant that the ITR sequences function as intended for the rescue, replication and packaging of the AAV vector. Hence, AAV ITRs for use in the gene delivery vectors of the present disclosure need not have a wild-type nucleotide sequence, and may be altered by the insertion, deletion or substitution of nucleotides or the AAV ITRs may be derived from any of several AAV serotypes, e.g. AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10. In some embodiments, the AAV ITR is derived from AAV1. In some embodiments, the AAV ITR is derived from AAV2. In some embodiments, the AAV ITR is derived from AAV3. In some embodiments, the AAV ITR is derived from AAV4. In some embodiments, the AAV ITR is derived from AAV5. In some embodiments, the AAV ITR is derived from AAV6. In some embodiments, the AAV ITR is derived from AAV7. In some embodiments, the AAV ITR is derived from AAV9. In some embodiments, the AAV ITR is derived from AAV10. In some embodiments, the rAAV vectors have the wild-type REP and CAP genes deleted in whole or part, but retain functional flanking ITR sequences. In some embodiments, the AAV ITR is one identified in Table 4. 037525.00573 [0171] In some embodiments, the rAAV vector comprises an AAV capsid, derived from any adeno-associated virus serotype known in the art, or prospectively discovered, including without limitation, AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, etc. For example, the AAV capsid may be a wild-type (or “native”) capsid. In some embodiments, the rAAV vector comprises an AAV capsid derived from AAV1. In some embodiments, the rAAV vector comprises an AAV capsid derived from AAV2. In some embodiments, the rAAV vector comprises an AAV capsid derived from AAV3. In some embodiments, the rAAV vector comprises an AAV capsid derived from AAV4. In some embodiments, the rAAV vector comprises an AAV capsid derived from AAV5. In some embodiments, the rAAV vector comprises an AAV capsid derived from AAV6. In some embodiments, the rAAV vector comprises an AAV capsid derived from AAV7. In some embodiments, the rAAV vector comprises an AAV capsid derived from AAV8. In some embodiments, the rAAV vector comprises an AAV capsid derived from AAV9. In some embodiments, the rAAV vector comprises an AAV capsid derived from AAV10. AAV capsids of particular interest include AAV2, AAV5, AAV8, and AAV9 (Table 5). However, as with the ITRs, the capsid need not have a wild-type nucleotide sequence, but rather may be altered by the insertion, deletion or substitution of nucleotides in the VP1, VP2 or VP3 sequence, so long as the capsid is able to transduce cells of the eye and/or lacrimal glands. Put another way, the AAV capsid may be a variant AAV capsid. In some embodiments, the rAAV vector is a “pseudotyped” AAV created by using the capsid (cap) gene of one AAV and the rep gene and ITRs from a different AAV, e.g. a pseudotyped AAV2 created by using rep from AAV2 and cap from AAV1, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, or AAV9 together with a plasmid containing a vector based on AAV2. For example, the rAAV vector may be rAAV2/1, rAAV2/3, rAAV2/4, rAAV2/5, rAAV2/6, rAAV2/7, rAAV2/8, rAAV2/9, etc. In some 037525.00573 embodiments, the rAAV is rAAV2/1. In some embodiments, the rAAV is rAAV2/3. In some embodiments, the rAAV is rAAV2/4. In some embodiments, the rAAV is rAAV2/5. In some embodiments, the rAAV is rAAV2/6. In some embodiments, the rAAV is rAAV2/7. In some embodiments, the rAAV is rAAV2/8. In some embodiments, the rAAV is rAAV2/9. [0172] In some embodiments, the rAAV is replication defective, in that the rAAV vector cannot independently further replicate and package its genome. For example, when eye and/or lacrimal glands are transduced with rAAV vectors, the gene is expressed in the transduced eye and/or lacrimal gland, however, due to the fact that the transduced eye and/or lacrimal glands lack AAV rep and cap genes and accessory function genes, the rAAV is not able to replicate. [0173] In some embodiments, rAAV vectors of the present disclosure encapsulating the expression cassettes as described herein, can be produced using helper-free production. rAAVs are replication-deficient viruses and normally require components from a live helper virus, such as adenovirus, in a host cell for packaging of infectious rAAV vectors. rAAV helper-free production systems allow the production of infectious rAAV vectors without the use of a live helper virus. In the helper-free system, a host packaging cell line is co-transfected with three plasmids. A first plasmid contains adenovirus gene products (i.e. E2A, E4, and VA RNA genes) needed for the packaging of rAAV vectors. A second plasmid contains the required AAV genes (i.e., REP and CAP genes). A third plasmid contains the polynucleotide sequence encoding the oxidoreductase enzyme (e.g., TRX or PDI) or a functional variant thereof and a promoter flanked by ITRs. A host packaging cell line can be, for example, AAV-293 host cells. Suitable host cells contain additional components required for packaging infectious rAAV vectors that are not supplied by the plasmids. In some embodiments, the CAP genes can encode, for example, AAV capsid proteins as described herein. In some embodiments, the promoter is a promoter sequence as described herein. In some embodiments, the promoter sequence is a CAG sequence. In some embodiments, the polynucleotide encodes a protein which shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 1. In some embodiments, the polynucleotide encodes a protein which shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 25. In some embodiments, the polynucleotide comprises a sequence that shares at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with SEQ ID NO: 2. 037525.00573 [0174] AAV serotypes shown to infect the eye and/or lacrimal gland include AAV2, AAV5, AAV 5w8, and AAV9 (Rocha et al., supra). Exemplary amino acid and nucleotide sequences for the AAV capsid proteins are identified in Table 5. [0175] In some embodiments, the AAV capsid protein shares at least 95%, 98%, or 100% identity to the AAV2 VP1 protein (SEQ ID NO: 6). In some embodiments, the polynucleotide sequence encoding the AAV2 VP1 protein shares at least 95%, 98%, or 100% identity with SEQ ID NO: 7. In some embodiments, the AAV capsid protein shares at least 95%, 98%, or 100% identity to the AAV2 VP3 protein (SEQ ID NO: 8). In some embodiments, the polynucleotide sequence encoding the AAV2 VP3 protein shares at least 95%, 98%, or 100% identity with SEQ ID NO: 9. In some embodiments, the AAV capsid protein shares at least 95%, 98%, or 100% identity to the AAV5capsid protein (SEQ ID NO: 10). In some embodiments, the polynucleotide sequence encoding the AAV5 capsid protein shares at least 95%, 98%, or 100% identity with SEQ ID NO: 11. In some embodiments, the AAV capsid protein shares at least 95%, 98%, or 100% identity to the AAV8 capsid protein (SEQ ID NO: 12). In some embodiments, the polynucleotide sequence encoding the AAV8 capsid protein shares at least 95%, 98%, or 100% identity with SEQ ID NO: 13. In some embodiments, the AAV capsid protein shares at least 95%, 98%, or 100% identity to the AAV9 capsid protein (SEQ ID NO: 14). In some embodiments, the polynucleotide sequence encoding the AAV9 capsid protein shares at least 95%, 98%, or 100% identity with SEQ ID NO: 15. Table 5: AAV Capsid Sequences Exemplary rAAV Vectors [0176] In some embodiments, the rAAV vector comprises an AAV capsid. In some embodiments, an rAAV vector described herein comprises an expression cassette comprising a polynucleotide comprising a nucleotide sequence encoding TRX. In some embodiments, an rAAV vector described herein comprises an expression cassette comprising a polynucleotide comprising a nucleotide sequence encoding PDI. In some embodiments, an rAAV vector described herein comprises a bicistronic expression cassette comprising a polynucleotide comprising a nucleotide sequence encoding both TRX and PDI. In some embodiments, the 037525.00573 polynucleotide is operably linked to a promoter. In some embodiments, the rAAV vector comprises an AAV capsid and the expression cassette, wherein the expression cassette comprises a polynucleotide operatively linked to a promoter, wherein the polynucleotide comprises a nucleotide sequence encoding TRX. In some embodiments, the rAAV vector comprises an AAV capsid and the expression cassette, wherein the expression cassette comprises a polynucleotide operatively linked to a promoter, wherein the polynucleotide comprises a nucleotide sequence encoding PDI. In some embodiments, the promoter is any described herein or known in the art. In some embodiments, the promoter is a CAG promoter. In some embodiments, the promoter is a CMV promoter. In some embodiments, the expression cassette further comprises a 5ʹITR and/or a 3ʹITR. In some embodiments, the 5ʹITR is an AAV2 5ʹITR. In some embodiments, the 3ʹITR is a AAV2 3ʹITR. In some embodiments, the expression cassette comprises a nucleotide sequence comprising from 5ʹ to 3ʹ: a 5ʹITR (e.g., an AAV2 5ʹITR), a promoter (e.g., a CMV promoter), a 5ʹuntranslated region (5ʹUTR), a polynucleotide sequence comprising a nucleotide sequence encoding a TRX enzyme, a polyA sequence, and a 3ʹITR (e.g., an AAV23ʹITR). In some embodiments, the expression cassette comprises a nucleotide sequence comprising from 5ʹ to 3ʹ: a 5ʹITR (e.g., an AAV25ʹITR), an enhancer (e.g., a CMV enhancer), a promoter (e.g., a CMV promoter), a 5ʹUTR, a polynucleotide sequence comprising a nucleotide sequence encoding a TRX enzyme, a WPRE sequence, a polyA sequence, and a 3ʹITR (e.g., an AAV23ʹITR). In some embodiments, the 5ʹUTR comprises a Kozak sequence positioned immediately upstream of and adjacent to an initiation codon in the nucleotide sequence encoding the TRX enzyme. [0177] In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter, wherein the polynucleotide comprises a nucleotide sequence encoding a human TRX enzyme described herein. In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a CAG promoter or a CMV promoter, wherein the polynucleotide comprises a nucleotide sequence encoding a TRX enzyme described herein. In some embodiments, the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotides sequence encoding a TRX enzyme described herein. [0178] In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a 037525.00573 nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 1. In some embodiments, the TRX enzyme comprises or consists of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 25. In some embodiments, the TRX enzyme comprises or consists of the amino acid sequence set forth in SEQ ID NO: 25. In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 2 or SEQ ID NO: 28. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 2. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 28. [0179] In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 25. In some embodiments, the TRX enzyme comprises or consists of the amino acid sequence set forth in SEQ ID NO: 25. 037525.00573 [0180] In some embodiments, the rAAV vector comprises an AAV2 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter, wherein the polynucleotide comprises a nucleotide sequence encoding a human TRX enzyme described herein. In some embodiments, the rAAV vector comprises an AAV2 capsid and an expression cassette comprising a polynucleotide operatively linked to a CAG promoter or a CMV promoter, wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme described herein. [0181] In some embodiments, the rAAV vector comprises an AAV2 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 1. In some embodiments, the TRX enzyme comprises or consists of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the rAAV vector comprises an AAV2 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 25. In some embodiments, the TRX enzyme comprises or consists of the amino acid sequence set forth in SEQ ID NO: 25. In some embodiments, the rAAV vector comprises an AAV2 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide encoding a TRX enzyme, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 2 or SEQ ID NO: 28. In some embodiments, the nucleotide 037525.00573 sequence comprises SEQ ID NO: 2. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 28. [0182] In some embodiments, the rAAV vector comprises an AAV5 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter, wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a human TRX enzyme described herein. In some embodiments, the rAAV vector comprises an AAV5 capsid and an expression cassette comprising a polynucleotide operatively linked to a CAG promoter, wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme described herein. [0183] In some embodiments, the rAAV vector comprises an AAV5 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 1. In some embodiments, the TRX enzyme comprises the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the rAAV vector comprises an AAV5 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 25. In some embodiments, the TRX enzyme comprises the amino acid sequence set forth in SEQ ID NO: 25. In some embodiments, the rAAV vector comprises an AAV5 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide encoding a TRX enzyme, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 037525.00573 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 2 or SEQ ID NO: 28. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 2. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 28. [0184] In some embodiments, the rAAV vector comprises an AAV9 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter, wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a human TRX enzyme described herein. In some embodiments, the rAAV vector comprises an AAV9 capsid and an expression cassette comprising a polynucleotide operatively linked to a CAG promoter, wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme described herein. [0185] In some embodiments, the rAAV vector comprises an AAV9 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 1. In some embodiments, the TRX enzyme comprises the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the rAAV vector comprises an AAV9 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a TRX enzyme, wherein the TRX enzyme comprises an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 25. In some embodiments, the TRX enzyme comprises the amino acid sequence set forth in SEQ ID NO: 25. In some embodiments, the rAAV vector comprises an AAV9 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide encoding a TRX enzyme, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, 037525.00573 at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 2 or SEQ ID NO: 28. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 2. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 28. [0186] In some embodiments, the promoter is any described herein or known in the art. In some embodiments, the promoter is a CAG promoter. In some embodiments, the promoter is a CMV promoter. In some embodiments, the expression cassette further comprises a 5ʹITR and/or a 3ʹITR. In some embodiments, the 5ʹITR is an AAV25ʹITR. In some embodiments, the 3ʹITR is a AAV23ʹITR. In some embodiments, the expression cassette comprises a nucleotide sequence comprising from 5ʹ to 3ʹ: a 5ʹITR (e.g., an AAV25ʹITR), a promoter (e.g., a CMV promoter), a 5ʹuntranslated region (5ʹUTR), a polynucleotide sequence comprising a nucleotide sequence encoding a PDI, a polyA sequence, and a 3ʹITR (e.g., an AAV2 3ʹITR). In some embodiments, the expression cassette comprises a nucleotide sequence comprising from 5ʹ to 3ʹ: a 5ʹITR (e.g., an AAV25ʹITR), an enhancer (e.g., a CMV enhancer), a promoter (e.g., a CMV promoter), a 5ʹUTR, a polynucleotide sequence comprising a nucleotide sequence encoding a PDI, a WPRE sequence, a polyA sequence, and a 3ʹITR (e.g., an AAV23ʹITR). In some embodiments, the 5ʹUTR comprises a Kozak sequence positioned immediately upstream of and adjacent to an initiation codon in the nucleotide sequence encoding the PDI. [0187] In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter, wherein the polynucleotide comprises a nucleotide sequence encoding a human PDI described herein. In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a CAG promoter or a CMV promoter, wherein the polynucleotide comprises a nucleotide sequence encoding a PDI described herein. [0188] In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises a nucleotide sequence encoding a PDI, wherein the PDI comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises or consists of the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a 037525.00573 polynucleotide operatively linked to a promoter (e.g., a CAG promoter), wherein the polynucleotide comprises a nucleotide sequence encoding a PDI, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 30. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 30. [0189] In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises a nucleotide sequence encoding a PDI, wherein the PDI comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises or consists of the amino acid sequence set forth in SEQ ID NO: 26. [0190] In some embodiments, the rAAV vector comprises an AAV2 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter, wherein the polynucleotide comprises a nucleotide sequence encoding a human PDI described herein. In some embodiments, the rAAV vector comprises an AAV2 capsid and an expression cassette comprising a polynucleotide operatively linked to a CAG promoter or a CMV promoter, wherein the polynucleotide comprises a nucleotide sequence encoding a PDI described herein. [0191] In some embodiments, the rAAV vector comprises an AAV2 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises a nucleotide sequence encoding a PDI, wherein the PDI comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises or consists of the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the rAAV vector comprises an AAV2 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises a nucleotide encoding a PDI, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at 037525.00573 least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 30. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 30. [0192] In some embodiments, the rAAV vector comprises an AAV5 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter, wherein the polynucleotide comprises a nucleotide sequence encoding a human PDI described herein. In some embodiments, the rAAV vector comprises an AAV5 capsid and an expression cassette comprising a polynucleotide operatively linked to a CAG promoter, wherein the polynucleotide comprises a nucleotide sequence encoding a PDI described herein. [0193] In some embodiments, the rAAV vector comprises an AAV5 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises a nucleotide sequence encoding a PDI, wherein the PDI comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the rAAV vector comprises an AAV5 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises a nucleotide encoding a PDI, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 30. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 30. [0194] In some embodiments, the rAAV vector comprises an AAV9 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter, wherein the polynucleotide comprises a nucleotide sequence encoding a human PDI described herein. In some embodiments, the rAAV vector comprises an AAV9 capsid and an expression cassette comprising a polynucleotide operatively linked to a CAG promoter, wherein the polynucleotide comprises a nucleotide sequence encoding a PDI described herein. [0195] In some embodiments, the rAAV vector comprises an AAV9 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises a nucleotide sequence encoding a PDI, wherein the PDI comprises an amino acid sequence that shares at least 85%, 037525.00573 at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the rAAV vector comprises an AAV9 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises a nucleotide encoding a PDI, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 30. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 30. [0196] In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a PDI, wherein the PDI comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises or consists of the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a PDI, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 30. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 30. [0197] In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter, wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a PDI, wherein the PDI comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, 037525.00573 at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises or consists of the amino acid sequence set forth in SEQ ID NO: 26. [0198] In some embodiments, the rAAV vector comprises an AAV2 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a PDI, wherein the PDI comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises or consists of the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the rAAV vector comprises an AAV2 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises a nucleotide encoding a PDI, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 30. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 30. [0199] In some embodiments, the rAAV vector comprises an AAV5 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a PDI, wherein the PDI comprises or consists of an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the rAAV vector comprises an AAV5 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises a nucleotide encoding a PDI, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or 037525.00573 at least 99% identity to SEQ ID NO: 30. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 30. [0200] In some embodiments, the rAAV vector comprises an AAV9 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises from 5ʹ to 3ʹ (i) a nucleotide sequence encoding a signal peptide, and (ii) a nucleotide sequence encoding a PDI, wherein the PDI comprises an amino acid sequence that shares at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 26. In some embodiments, the PDI comprises the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the rAAV vector comprises an AAV9 capsid and an expression cassette comprising a polynucleotide operatively linked to a promoter (e.g., a CAG promoter or CMV promoter), wherein the polynucleotide comprises a nucleotide encoding a PDI, wherein the nucleotide sequence comprises a nucleotide sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 30. In some embodiments, the nucleotide sequence comprises SEQ ID NO: 30. Methods of Use [0201] Methods and compositions described herein can be used to treat ocular conditions and reduce the associated symptoms of the ocular conditions. The terms “treatment”, “treating” and the like are used herein to generally mean obtaining a desired pharmacologic and/or physiologic effect. The effect may be prophylactic in terms of completely or partially preventing a disease or symptom thereof, e.g. reducing the likelihood that the disease or symptom thereof occurs in the subject, delaying the onset or progression of a disease or a symptom in a subject and/or may be therapeutic in terms of a partial or complete cure for a disease and/or adverse effect attributable to the disease. “Treatment” as used herein covers any treatment of a disease in a mammal, and includes, without limitation: (a) inhibiting progress of the disease; (b) alleviating, reducing, or reducing an increase in one or more symptoms of the disease; (c) alleviating, reducing, or reducing an increase in one or more signs of the disease; (d) causing regression of the disease. The therapeutic agent may be administered before, during or after the onset of disease or injury. The treatment of ongoing disease, where the treatment 037525.00573 stabilizes or reduces the undesirable clinical symptoms of the patient, is of particular interest. Such treatment is desirably performed prior to complete loss of function in the affected tissues. The subject therapy will desirably be administered during the symptomatic stage of the disease, and in some cases after the symptomatic stage of the disease. [0202] As used herein, “administer,” “administering,” “administration” and the like refers to providing a substance (e.g., rAAV vector) to a subject in a manner that is pharmacologically useful (e.g., to treat a disease, disorder, or condition in the subject). [0203] Thus, in some embodiments, provided herein are methods of treating an ocular condition in a subject, the method comprising administering to the subject an rAAV vector provided herein or a pharmaceutical composition provided herein. As herein, the terms “subject” and “patient” are used interchangeably to refer to a mammal, including, but not limited to, human and non-human primates, including simians and humans; mammalian sport animals (e.g., horses); mammalian farm animals (e.g., sheep, goats, etc.); mammalian pets (dogs, cats, etc.); and rodents (e.g., mice, rats, etc.). A subject can have, for example, any of the symptoms or ocular disorders described herein. [0204] In some embodiments, the subject is a human adult, e.g., a human adult over the age of 40 or a human adult 45 to 55 years of age. In some embodiments, the subject is a human adult over the age of 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90. [0205] In some embodiments, the ocular condition treated in accordance with the methods described herein is a disorder that is associated with increased oxidative stress. In some embodiments, the condition is associated with loss of expression or function of one or more oxidoreductase enzymes. In some embodiments, the condition is associated with loss of protein disulfide isomerase (PDI) expression and/or function. In some embodiments, the condition is associated with loss of TRX expression and/or function. Without wishing to be bound by theory, it is hypothesized that increased expression of TRX, PDI, and/or other oxidoreductase enzymes can reduce oxidative stress in a tissue and thus slow down the ageing process and prolong the onset of conditions associated with, or caused by, ageing. In some embodiments, the condition is associated with loss of near vision, e.g., the gradual loss of ability to focus the eye on nearby objects. In some embodiments, the condition is cataract formation. In some embodiments, the condition is loss of accommodation. In some embodiments, the condition is presbyopia. In some embodiments, the condition is meibomian gland dysfunction (MGD). In some embodiments, the condition is ocular hypertension. In some embodiments, the condition 037525.00573 is glaucoma. In some embodiments, neural protection is provided by the methods described herein. [0206] In some embodiments, a method of treatment described herein comprises further administering to the subject one or more addition therapeutic agents. In some embodiments, the additional therapeutic agent is an agent that increases tear production. In some embodiments, the additional therapeutic agent that increases tear production is a cholinergic agonist. In some embodiments, the additional therapeutic agent is another AAV-based gene therapy construct. Agents for Tear Production [0207] In some embodiments, the treatment that increases tear production comprises administering an effective amount of a nicotinic acetylcholine receptor (nAChR) agonist, or a pharmaceutically acceptable salt thereof. In some embodiments, the nAChR agonist is one described herein. [0208] nAChRs are a class of pentameric ligand-gated ion channels that have high affinity and selectivity for both nicotine and acetylcholine (which resembles nicotine in its protonated form) and comprise combinations of alpha and beta subunits. Examples of nAChR subtypes include, but are not limited to, alpha3beta4, alpha4beta2, alpha3alpha5beta4, and alpha4alpha6beta2. [0209] A nAChR agonist may be characterized as a full or partial agonist as determined by its ability to activate a given receptor to produce a response as compared to the response at that receptor for acetylcholine (ACh). In general, a nAChR agonist is a full agonist if it evokes a response upon binding to a given receptor that is equal or greater to that of ACh. A nAChR agonist is a partial agonist if it evokes a lower response upon binding to the receptor as compared to the response generated from ACh. [0210] nAChR agonist response, from which receptor activation can be determined can, for example, be generated using an appropriate cell-based assay. Cells designed to express a particular nAChR receptor subtype and generate an electrical current response when bound to and activated by a nAChR agonist can be used to characterize the agonist profile of a compound and the amount of receptor activation thus determined. [0211] In some embodiments, the nAChR agonist, or a pharmaceutically acceptable salt thereof, selectively binds to at least one of the nAChR subtypes selected from alpha3beta4, alpha3alpha5beta4, alpha4beta2, and alpha4alpha6beta2. As used herein, “selectively binds” or “is selective for” means that a compound has a higher affinity for the nAChR subtype and/or 037525.00573 a lower half-maximal effective concentration (EC50) for that nAChr subtype for at least one reference nAChR subtype. Selectivity may be associated with at least a 5-fold affinity difference in EC50 value, at least a 10-fold affinity difference in EC50 value, at least a 20-fold affinity difference in EC50 value, or at least a 50-fold affinity difference in EC50 value. In some embodiments, the nAChR agonist, or a pharmaceutically acceptable salt thereof, selectively binds to nAChR subtype alpha3beta4. In some embodiments, the nAChR agonist, or a pharmaceutically acceptable salt thereof, selectively binds to nAChR subtype alpha3alpha5beta4. In some embodiments, the nAChR agonist, or a pharmaceutically acceptable salt thereof, selectively binds to nAChR subtype alpha4beta2. In some embodiments, the nAChR agonist, or a pharmaceutically acceptable salt thereof, selectively binds to nAChR subtype alpha4alpha6beta2. In some embodiments, the nAChR agonist, or a pharmaceutically acceptable salt thereof, selectively binds to nAChR subtype alpha7. In some embodiments, the nAChR agonist, or a pharmaceutically acceptable salt thereof, does not selectively bind to nAChR subtype alpha7. [0212] The nAChR agonists contemplated in this disclosure include varenicline, a pharmaceutically acceptable salt thereof, and compound 1, or a pharmaceutically acceptable salt thereof. In some embodiments the nAChR agonist is not varenicline. [0213] Varenicline is characterized as a full agonist of the nAChR subtype alpha7 and a partial agonist of subtypes alpha3beta4, alpha4beta2, alpha6beta2, alpha3alpha5beta4, and alpha4alpha6beta2. In some embodiments, the nAChR agonist is varenicline, or a pharmaceutically acceptable salt thereof. Pharmaceutically acceptable salts of varenicline include varenicline tartrate. Additional related information for varenicline may be found in, for example, U.S. Patent 6,951,938, U.S. Patent 6,890,927, U.S. Patent 7,265,119, U.S. Patent 9,504,644, U.S. Patent 9,504,645, U.S. Patent 9,532,944, U.S. Patent 9,597,284, U.S. Patent 10,456,386, U.S. Patent 11,224,598, and U.S. Application Publication 2022/0233528. [0214] Compound 1, as recited herein, refers to the structure: [0215] An alternative structural representation of compound 1 is shown here: 037525.00573 [0216] Compound 1 may be also referred to by its chemical name. For instance, compound 1 is also referred to as (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or variations thereof including simpanicline, 5-{(E)-2-[(3R)-pyrrolidin-3-yl]vinyl}pyrimidine and (R,E)-5-((2- pyrrolidine-3-yl)vinyl)pyrimidine. [0217] Compound 1 is a full agonist of nAChR subtypes alpha4beta2, alpha3beta4, alpha3alpha5beta4, and alpha4alpha6beta2. Compound 1 is a full agonist of nAChR subtypes alpha4beta2, and alpha3beta4. [0218] Compound 1 is a partial agonist of subtype alpha3beta2. [0219] Compound 1 is a weak partial agonist of subtype alpha7. In one example, a 300 micromolar concentration of compound 1 citrate evoked only 25% of the maximal ACh-evoked current. [0220] In some embodiments, the nAChR agonist may be compound 1, or a pharmaceutically acceptable salt thereof. Pharmaceutically acceptable salts of compound 1 include galactarate (e.g., hemi-galactarate dihydrate) and citrate (e.g., mono-citrate). Patent related information for compound 1 may be found in e.g., U.S. Patent 7,098,331, U.S. Patent 7,714,001, U.S. Patent 8,063,068, U.S. Patent 8,067,443, U.S. Patent 8,604,191, U.S. Patent 9,145,396, U.S. Patent 9,981,949, U.S. Patent 8,633,222, U.S. Patent 8,153,821, U.S. Patent 8,633,227, U.S. Patent 10,709,707, U.S. Patent Application Publication 2020-0345734, and PCT publication WO 2017/177024. [0221] In some embodiments, the nAChR agonist is (R)-5-((E)-2-pyrrolidin-3- ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof. In some embodiments, the nAChR agonist is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemigalactarate dihydrate. In some embodiments, the nAChR agonist is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono- citrate. [0222] In some embodiments, the nAChR agonist increases tear production in a subject where tear secretion is compromised. Methods of Treatment [0223] In some embodiments, the disclosure provides a method of treating a subject with an ocular disease or disorder, comprising administering to the subject an rAAV comprising a nucleotide encoding human TRX described herein, wherein expression of the human TRX is 037525.00573 increase in the subject compared to expression of the human TRX in an untreated subject, or in the contralateral eye of a treated subject. [0224] In some embodiments, the disclosure provides rAAV vectors for use in a method of treating an ocular condition in a subject in need thereof, the method comprising administering a recombinant adeno-associated virus (rAAV) vector, the rAAV vector comprising an AAV capsid and an expression cassette comprising a polynucleotide encoding human TRX operatively linked to a promoter, to at least one eye of the subject, at least one lacrimal gland of the eye of the subject, or at least on the meibomian gland of the subject. In some embodiments, the rAAV vector for use is administered to the lacrimal gland of a subject. In some embodiments, the rAAV vector for use comprises an expression cassette encoding human TRX. [0225] In some embodiments, the disclosure provides rAAV vector for use, or adaptable for use, to treat a subject with an ocular disease, disorder, or condition. In some embodiments, the rAAV vector for use or adaptable for use comprise an AAV capsid and an expression cassette comprising a polynucleotide encoding human TRX operatively linked to a promoter. [0226] In some embodiments, the disclosure provides rAAV vectors for use in a method of treating an ocular condition in a subject in need thereof, the method comprising administering a recombinant adeno-associated virus (rAAV) vector described herein to at least one eye of the subject or to at least one lacrimal gland of the eye of the subject. [0227] In some embodiments, the disclosure provides rAAV vectors for use in a method of treating an ocular condition in a subject in need thereof, the method comprising administering a recombinant adeno-associated virus (rAAV) vector comprising an expression cassette comprising the nucleic acid sequence of SEQ ID NO: 16 to at least one eye of the subject or to at least one lacrimal gland of the eye of the subject. [0228] In some embodiments, expression of the human TRX is increased 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% compared to expression of human TRX in an untreated subject, or in the contralateral eye of a treated subject. In some embodiments, expression of human TRX is increased by at least 1.5-fold, 2-fold, 3-fold, 4-fold, or 5-fold, 6-fold, 7-fold, 8-fold, or 9-fold compared to expression of human TRX in an untreated subject, or in the contralateral eye of a treated subject. [0229] In some embodiments, expression of the human TRX is increased for about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 037525.00573 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 1 year compared to expression of the human TRX in an untreated subject, or in the contralateral eye of a treated subject. [0230] As used herein, “approximately” or “about,” as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In certain embodiments, “about” refers to a range of values that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value). [0231] In some embodiments, a subject is administered an rAAV comprising a nucleotide encoding human TRX enzyme described herein, wherein expression of the human TRX enzyme is increase in the subject compared to expression of human TRX in an untreated subject, or in the contralateral eye of a treated subject. [0232] In some embodiments, expression of the human TRX enzyme is increased 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% compared to expression of the human TRX enzyme in an untreated subject, or in the contralateral eye of a treated subject. In some embodiments, expression of the human TRX enzyme may be increased at least 1.5-fold, 2-fold, 3-fold, 4-fold, or 5-fold, 6-fold, 7-fold, 8- fold, or 9-fold compared to expression of the human TRX enzyme in an untreated subject, or in the contralateral eye of a treated subject. [0233] In some embodiments, expression of the human TRX enzyme is increased for about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 1 year compared to expression of the human TRX enzyme in an untreated subject, or in the contralateral eye of a treated subject. [0234] In some embodiments, the disclosure provides a method of treating a subject with an ocular disease or disorder, comprising administering to the subject an rAAV comprising a nucleotide encoding a human TRX enzyme, wherein expression of human TRX enzyme is increase in the subject compared to expression of human TRX enzyme in an untreated subject, or in the contralateral eye of a treated subject. [0235] In some embodiments, the disclosure provides a method of treating a subject with an ocular disease or disorder, comprising administering to the subject an rAAV comprising a nucleotide encoding human PDI described herein, wherein expression of the human PDI is 037525.00573 increase in the subject compared to expression of the human PDI in an untreated subject, or in the contralateral eye of a treated subject. [0236] In some embodiments, the disclosure provides rAAV vectors for use in a method of treating an ocular condition in a subject in need thereof, the method comprising administering a recombinant adeno-associated virus (rAAV) vector, the rAAV vector comprising an AAV capsid and an expression cassette comprising a polynucleotide encoding human PDI operatively linked to a promoter, to at least one eye of the subject or to at least one lacrimal gland of the eye of the subject. In some embodiments, the rAAV vector for use is administered to the lacrimal gland of a subject. In some embodiments, the rAAV vector for use comprises an expression cassette encoding human PDI. [0237] In some embodiments, the disclosure provides rAAV vector for use, or adaptable for use, to treat a subject with an ocular disease, disorder, or condition. In some embodiments, the rAAV vector for use or adaptable for use comprise an AAV capsid and an expression cassette comprising a polynucleotide encoding human PDI operatively linked to a promoter. [0238] In some embodiments, the disclosure provides rAAV vectors for use in a method of treating an ocular condition in a subject in need thereof, the method comprising administering a recombinant adeno-associated virus (rAAV) vector described herein to at least one eye of the subject or to at least one lacrimal gland of the eye of the subject. [0239] In some embodiments, the disclosure provides rAAV vectors for use in a method of treating an ocular condition in a subject in need thereof, the method comprising administering a recombinant adeno-associated virus (rAAV) vector comprising an expression cassette comprising the nucleic acid sequence of SEQ ID NO: 16 to at least one eye of the subject or to at least one lacrimal gland of the eye of the subject. [0240] In some embodiments, expression of the human PDI is increased 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% compared to expression of human PDI in an untreated subject, or in the contralateral eye of a treated subject. In some embodiments, expression of human PDI is increased by at least 1.5-fold, 2-fold, 3-fold, 4-fold, or 5-fold, 6-fold, 7-fold, 8-fold, or 9-fold compared to expression of human PDI in an untreated subject, or in the contralateral eye of a treated subject. [0241] In some embodiments, expression of the human PDI is increased for about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 1 year compared to expression of the human PDI in an untreated subject, or in 037525.00573 the contralateral eye of a treated subject. [0242] In some embodiments, a subject is administered an rAAV comprising a nucleotide encoding human PDI described herein, wherein expression of the human PDI is increase in the subject compared to expression of human PDI in an untreated subject, or in the contralateral eye of a treated subject. [0243] In some embodiments, expression of the human PDI is increased 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% compared to expression of the human PDI in an untreated subject, or in the contralateral eye of a treated subject. In some embodiments, expression of the human PDI may be increased at least 1.5-fold, 2-fold, 3-fold, 4-fold, or 5-fold, 6-fold, 7-fold, 8-fold, or 9-fold compared to expression of the human PDI in an untreated subject, or in the contralateral eye of a treated subject. [0244] In some embodiments, expression of the human PDI is increased for about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 1 year compared to expression of the human PDI in an untreated subject, or in the contralateral eye of a treated subject. [0245] In some embodiments, the disclosure provides a method of treating a subject with an ocular disease or disorder, comprising administering to the subject an rAAV comprising a nucleotide encoding a human PDI, wherein expression of human PDI is increase in the subject compared to expression of human PDI in an untreated subject, or in the contralateral eye of a treated subject. [0246] In some embodiments, the method comprises administering a dose of the rAAV to a subject having a condition associated with cataract formation, wherein the condition is characterized by one or more symptoms described herein. In some embodiments, the dose is administered prior to the onset of the one or more symptoms. In some embodiments, the administering prevents the onset of the one or more symptoms. In some embodiments, the administering reduces the severity of the one or more symptoms. For example, in some embodiments, the method comprises administering a dose of the rAAV to a subject having cataract formation characterized by one or more symptoms (e.g., blurry vision, double vision, faded color vision, difficulty seeing at night), wherein the dose of the rAAV is administered and prevents or lessens the severity of the one or more symptoms. In some embodiments, the 037525.00573 dose is administered following the onset of the one or more symptoms, wherein the administering reduces the severity of the one or more symptoms. [0247] In some embodiments, the method comprises administering a dosing regimen of the rAAV to a subject having a condition associated with cataract formation, wherein the condition is characterized by one or more symptoms described herein (e.g., blurry vision, double vision, faded color vision, difficulty seeing at night), wherein the dosing regimen comprises a first dose of the rAAV and at least one additional dose, wherein the first dose of the rAAV is administered to the subject prior to or subsequent to the onset of the one or more symptoms, and wherein the at least one additional dose is administered to the subject following the first dose, thereby preventing or reducing the severity of the one or more symptoms. In some embodiments, the dosing regimen comprises a frequency of dosing and/or dose amount that is selected based upon the pharmacokinetic parameters of the rAAV. In some embodiments, a clinician will administer the rAAV at a frequency and/or dose that achieves or maintains one or more desired effects. In some embodiments, the one or more desired effects is preventing one or more symptoms associated with the subject’s condition. In some embodiments, the one or more desired effects is reducing the severity of one or more symptoms associated with the subject’s condition. In some embodiments, the severity of the one or more symptoms is measured using a method described herein or known in the art for evaluating a pathology associated with cataract formation. In some embodiments, the one or more desired effects is achieved immediately following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects occurs at any time point following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects is achieved following administration of the at least one additional dose of the rAAV. In some embodiments, the one or more desired effects is achieved at any point during the dosing regimen. In some embodiments, the one or more desired effects is achieved following administration of the first dose of the rAAV and the subject is administered at least one additional dose of the rAAV to prevent reversal of the one or more desired effects. In some embodiments, the method comprises administering a first dose of the rAAV to the subject prior to, immediately following, or during the onset of one or more symptoms and an additional dose following a duration of about 1 week, about 2 weeks, about 3 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, about 1.5 years, or about 2 years after the first dose. 037525.00573 [0248] In some embodiments, the method comprises reversing cataract formation. In some embodiments, the method comprises administering a dose of rAAV to a subject having cataract formation, wherein administration reverses cataract formation. [0249] In some embodiments, the method comprises administering a dose of the rAAV to a subject having a condition associated with presbyopia, wherein the condition is characterized by one or more symptoms described herein. In some embodiments, the dose is administered prior to the onset of the one or more symptoms. In some embodiments, the administering prevents the onset of the one or more symptoms. In some embodiments, the administering reduces the severity of the one or more symptoms. For example, in some embodiments, the method comprises administering a dose of the rAAV to a subject having presbyopia characterized by one or more symptoms (e.g., blurry vision, trouble reading, headaches), wherein the dose of the rAAV is administered and prevents or lessens the severity of the one or more symptoms. In some embodiments, the dose is administered following the onset of the one or more symptoms, wherein the administering reduces the severity of the one or more symptoms. [0250] In some embodiments, the method comprises administering a dosing regimen of the rAAV to a subject having a condition associated with presbyopia, wherein the condition is characterized by one or more symptoms described herein (e.g., blurry vision, trouble reading, headaches), wherein the dosing regimen comprises a first dose of the rAAV and at least one additional dose, wherein the first dose of the rAAV is administered to the subject prior to or subsequent to the onset of the one or more symptoms, and wherein the at least one additional dose is administered to the subject following the first dose, thereby preventing or reducing the severity of the one or more symptoms. In some embodiments, the dosing regimen comprises a frequency of dosing and/or dose amount that is selected based upon the pharmacokinetic parameters of the rAAV. In some embodiments, a clinician will administer the rAAV at a frequency and/or dose that achieves or maintains one or more desired effects. In some embodiments, the one or more desired effects is preventing one or more symptoms associated with the subject’s condition. In some embodiments, the one or more desired effects is reducing the severity of one or more symptoms associated with the subject’s condition. In some embodiments, the severity of the one or more symptoms is measured using a method described herein or known in the art for evaluating a pathology associated with presbyopia. In some embodiments, the one or more desired effects is achieved immediately following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects occurs at 037525.00573 any time point following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects is achieved following administration of the at least one additional dose of the rAAV. In some embodiments, the one or more desired effects is achieved at any point during the dosing regimen. In some embodiments, the one or more desired effects is achieved following administration of the first dose of the rAAV and the subject is administered at least one additional dose of the rAAV to prevent reversal of the one or more desired effects. In some embodiments, the method comprises administering a first dose of the rAAV to the subject prior to, immediately following, or during the onset of one or more symptoms and an additional dose following a duration of about 1 week, about 2 weeks, about 3 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, about 1.5 years, or about 2 years after the first dose. [0251] In some embodiments, the method comprises administering a dose of the rAAV to a subject having a condition associated with loss of accommodation, wherein the condition is characterized by one or more symptoms described herein. In some embodiments, the dose is administered prior to the onset of the one or more symptoms. In some embodiments, the administering prevents the onset of the one or more symptoms. In some embodiments, the administering reduces the severity of the one or more symptoms. For example, in some embodiments, the method comprises administering a dose of the rAAV to a subject having loss of accommodation characterized by one or more symptoms (e.g., blurry vision, trouble reading, headaches), wherein the dose of the rAAV is administered and prevents or lessens the severity of the one or more symptoms. In some embodiments, the dose is administered following the onset of the one or more symptoms, wherein the administering reduces the severity of the one or more symptoms. [0252] In some embodiments, the method comprises administering a dosing regimen of the rAAV to a subject having a condition associated with loss of accommodation, wherein the condition is characterized by one or more symptoms described herein (e.g., blurry vision, trouble reading, headaches), wherein the dosing regimen comprises a first dose of the rAAV and at least one additional dose, wherein the first dose of the rAAV is administered to the subject prior to or subsequent to the onset of the one or more symptoms, and wherein the at least one additional dose is administered to the subject following the first dose, thereby preventing or reducing the severity of the one or more symptoms. In some embodiments, the dosing regimen comprises a frequency of dosing and/or dose amount that is selected based 037525.00573 upon the pharmacokinetic parameters of the rAAV. In some embodiments, a clinician will administer the rAAV at a frequency and/or dose that achieves or maintains one or more desired effects. In some embodiments, the one or more desired effects is preventing one or more symptoms associated with the subject’s condition. In some embodiments, the one or more desired effects is reducing the severity of one or more symptoms associated with the subject’s condition. In some embodiments, the severity of the one or more symptoms is measured using a method described herein or known in the art for evaluating a pathology associated with loss of accommodation. In some embodiments, the one or more desired effects is achieved immediately following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects occurs at any time point following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects is achieved following administration of the at least one additional dose of the rAAV. In some embodiments, the one or more desired effects is achieved at any point during the dosing regimen. In some embodiments, the one or more desired effects is achieved following administration of the first dose of the rAAV and the subject is administered at least one additional dose of the rAAV to prevent reversal of the one or more desired effects. In some embodiments, the method comprises administering a first dose of the rAAV to the subject prior to, immediately following, or during the onset of one or more symptoms and an additional dose following a duration of about 1 week, about 2 weeks, about 3 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, about 1.5 years, or about 2 years after the first dose. [0253] In some embodiments, the method comprises administering a dose of the rAAV to a subject having a condition associated with ocular hypertension, wherein the condition is characterized by one or more symptoms described herein. In some embodiments, the dose is administered prior to the onset of the one or more symptoms. In some embodiments, the administering prevents the onset of the one or more symptoms. In some embodiments, the administering reduces the severity of the one or more symptoms. For example, in some embodiments, the method comprises administering a dose of the rAAV to a subject having ocular hypertension characterized by one or more symptoms (e.g., eye pain, nausea, vomiting), wherein the dose of the rAAV is administered and prevents or lessens the severity of the one or more symptoms. In some embodiments, the dose is administered following the onset of the 037525.00573 one or more symptoms, wherein the administering reduces the severity of the one or more symptoms. [0254] In some embodiments, the method comprises administering a dosing regimen of the rAAV to a subject having a condition associated with ocular hypertension, wherein the condition is characterized by one or more symptoms described herein (e.g., eye pain, nausea, vomiting), wherein the dosing regimen comprises a first dose of the rAAV and at least one additional dose, wherein the first dose of the rAAV is administered to the subject prior to or subsequent to the onset of the one or more symptoms, and wherein the at least one additional dose is administered to the subject following the first dose, thereby preventing or reducing the severity of the one or more symptoms. In some embodiments, the dosing regimen comprises a frequency of dosing and/or dose amount that is selected based upon the pharmacokinetic parameters of the rAAV. In some embodiments, a clinician will administer the rAAV at a frequency and/or dose that achieves or maintains one or more desired effects. In some embodiments, the one or more desired effects is preventing one or more symptoms associated with the subject’s condition. In some embodiments, the one or more desired effects is reducing the severity of one or more symptoms associated with the subject’s condition. In some embodiments, the severity of the one or more symptoms is measured using a method described herein or known in the art for evaluating a pathology associated with ocular hypertension. In some embodiments, the one or more desired effects is achieved immediately following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects occurs at any time point following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects is achieved following administration of the at least one additional dose of the rAAV. In some embodiments, the one or more desired effects is achieved at any point during the dosing regimen. In some embodiments, the one or more desired effects is achieved following administration of the first dose of the rAAV and the subject is administered at least one additional dose of the rAAV to prevent reversal of the one or more desired effects. In some embodiments, the method comprises administering a first dose of the rAAV to the subject prior to, immediately following, or during the onset of one or more symptoms and an additional dose following a duration of about 1 week, about 2 weeks, about 3 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, about 1.5 years, or about 2 years after the first dose. 037525.00573 [0255] In some embodiments, the method comprises administering a dose of the rAAV to a subject having a condition associated with meibomian gland dysfunction (MDI), wherein the condition is characterized by one or more symptoms described herein. In some embodiments, the dose is administered prior to the onset of the one or more symptoms. In some embodiments, the administering prevents the onset of the one or more symptoms. In some embodiments, the administering reduces the severity of the one or more symptoms. For example, in some embodiments, the method comprises administering a dose of the rAAV to a subject having meibomian gland dysfunction (MDI) characterized by one or more symptoms (e.g., eye dryness, burning, itching, redness, discharge, blurry vision), wherein the dose of the rAAV is administered and prevents or lessens the severity of the one or more symptoms. In some embodiments, the dose is administered following the onset of the one or more symptoms, wherein the administering reduces the severity of the one or more symptoms. [0256] In some embodiments, the method comprises administering a dosing regimen of the rAAV to a subject having a condition associated with meibomian gland dysfunction (MDI), wherein the condition is characterized by one or more symptoms described herein (e.g., eye dryness, burning, itching, redness, discharge, blurry vision), wherein the dosing regimen comprises a first dose of the rAAV and at least one additional dose, wherein the first dose of the rAAV is administered to the subject prior to or subsequent to the onset of the one or more symptoms, and wherein the at least one additional dose is administered to the subject following the first dose, thereby preventing or reducing the severity of the one or more symptoms. In some embodiments, the dosing regimen comprises a frequency of dosing and/or dose amount that is selected based upon the pharmacokinetic parameters of the rAAV. In some embodiments, a clinician will administer the rAAV at a frequency and/or dose that achieves or maintains one or more desired effects. In some embodiments, the one or more desired effects is preventing one or more symptoms associated with the subject’s condition. In some embodiments, the one or more desired effects is reducing the severity of one or more symptoms associated with the subject’s condition. In some embodiments, the severity of the one or more symptoms is measured using a method described herein or known in the art for evaluating a pathology associated with meibomian gland dysfunction (MDI). In some embodiments, the one or more desired effects is achieved immediately following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects occurs at any time point following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects is achieved following administration of the at least one additional dose of the 037525.00573 rAAV. In some embodiments, the one or more desired effects is achieved at any point during the dosing regimen. In some embodiments, the one or more desired effects is achieved following administration of the first dose of the rAAV and the subject is administered at least one additional dose of the rAAV to prevent reversal of the one or more desired effects. In some embodiments, the method comprises administering a first dose of the rAAV to the subject prior to, immediately following, or during the onset of one or more symptoms and an additional dose following a duration of about 1 week, about 2 weeks, about 3 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, about 1.5 years, or about 2 years after the first dose. [0257] In some embodiments, the method comprises administering a dose of the rAAV to a subject having a condition associated with oxidative stress, wherein the condition is characterized by one or more symptoms described herein. In some embodiments, the dose is administered prior to the onset of the one or more symptoms. In some embodiments, the administering prevents the onset of the one or more symptoms. In some embodiments, the administering reduces the severity of the one or more symptoms. For example, in some embodiments, the method comprises administering a dose of the rAAV to a subject having oxidative stress characterized by one or more symptoms (e.g., oxidative stress leading to retinal degeneration, cataracts, or macular degeneration), wherein the dose of the rAAV is administered and prevents or lessens the severity of the one or more symptoms. In some embodiments, the dose is administered following the onset of the one or more symptoms, wherein the administering reduces the severity of the one or more symptoms. [0258] In some embodiments, the method comprises administering a dosing regimen of the rAAV to a subject having a condition associated with oxidative stress, wherein the condition is characterized by one or more symptoms described herein (e.g., oxidative stress leading to retinal degeneration, cataracts, or macular degeneration), wherein the dosing regimen comprises a first dose of the rAAV and at least one additional dose, wherein the first dose of the rAAV is administered to the subject prior to or subsequent to the onset of the one or more symptoms, and wherein the at least one additional dose is administered to the subject following the first dose, thereby preventing or reducing the severity of the one or more symptoms. In some embodiments, the dosing regimen comprises a frequency of dosing and/or dose amount that is selected based upon the pharmacokinetic parameters of the rAAV. In some embodiments, a clinician will administer the rAAV at a frequency and/or dose that achieves or 037525.00573 maintains one or more desired effects. In some embodiments, the one or more desired effects is preventing one or more symptoms associated with the subject’s condition. In some embodiments, the one or more desired effects is reducing the severity of one or more symptoms associated with oxidative stress. In some embodiments, the severity of the one or more symptoms is measured using a method described herein or known in the art for evaluating a pathology associated with oxidative stress. In some embodiments, the one or more desired effects is achieved immediately following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects occurs at any time point following administering of the first dose of the rAAV. In some embodiments, the one or more desired effects is achieved following administration of the at least one additional dose of the rAAV. In some embodiments, the one or more desired effects is achieved at any point during the dosing regimen. In some embodiments, the one or more desired effects is achieved following administration of the first dose of the rAAV and the subject is administered at least one additional dose of the rAAV to prevent reversal of the one or more desired effects. In some embodiments, the method comprises administering a first dose of the rAAV to the subject prior to, immediately following, or during the onset of one or more symptoms and an additional dose following a duration of about 1 week, about 2 weeks, about 3 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, about 1.5 years, or about 2 years after the first dose. [0259] In some embodiments, the disclosure provides a method for treating cataract formation in a subject in need thereof, the method comprising administering to the subject one or more therapeutically effective doses of an rAAV described herein. [0260] In some embodiments, the disclosure provides a method for treating presbyopia in a subject in need thereof, the method comprising administering to the subject one or more therapeutically effective doses of an rAAV described herein. [0261] In some embodiments, the disclosure provides a method for treating oxidative stress in a subject in need thereof, the method comprising administering to the subject one or more therapeutically effective doses of an rAAV described herein. [0262] In some embodiments, the disclosure provides a method for treating loss of accommodation in a subject in need thereof, the method comprising administering to the subject one or more therapeutically effective doses of an rAAV described herein. 037525.00573 [0263] In some embodiments, the disclosure provides a method for ocular treating hypertension in a subject in need thereof, the method comprising administering to the subject one or more therapeutically effective doses of an rAAV described herein. [0264] In some embodiments, the disclosure provides a method for treating meibomian gland dysfunction in a subject in need thereof, the method comprising administering to the subject one or more therapeutically effective doses of an rAAV described herein. [0265] In some embodiments, the disclosure provides an rAAV described herein for use in a method of treating a cataract formation in a subject in need thereof, the method comprising administering to the subject an effective amount of an rAAV described herein. [0266] In some embodiments, the disclosure provides an rAAV described herein for use in the manufacture of a medicament for treating a cataract formation in a subject in need thereof. [0267] In some embodiments, the disclosure provides an rAAV described herein for use in a method of treating presbyopia in a subject in need thereof, the method comprising administering to the subject an effective amount of an rAAV described herein. [0268] In some embodiments, the disclosure provides an rAAV described herein for use in the manufacture of a medicament for treating presbyopia in a subject in need thereof. [0269] In some embodiments, the disclosure provides an rAAV described herein for use in a method of treating loss of accommodation in a subject in need thereof, the method comprising administering to the subject an effective amount of an rAAV described herein. [0270] In some embodiments, the disclosure provides an rAAV described herein for use in the manufacture of a medicament for treating loss of accommodation in a subject in need thereof. [0271] In some embodiments, the disclosure provides an rAAV described herein for use in a method of treating oxidative stress in a subject in need thereof, the method comprising administering to the subject an effective amount of an rAAV described herein. [0272] In some embodiments, the disclosure provides an rAAV described herein for use in the manufacture of a medicament for treating oxidative stress in a subject in need thereof. [0273] In some embodiments, the disclosure provides an rAAV described herein for use in a method of treating ocular hypertension in a subject in need thereof, the method comprising administering to the subject an effective amount of an rAAV described herein. [0274] In some embodiments, the disclosure provides an rAAV described herein for use in the manufacture of a medicament for treating ocular hypertension in a subject in need thereof. 037525.00573 [0275] In some embodiments, the disclosure provides an rAAV described herein for use in a method of treating meibomian gland dysfunction in a subject in need thereof, the method comprising administering to the subject an effective amount of an rAAV described herein. [0276] In some embodiments, the disclosure provides an rAAV described herein for use in the manufacture of a medicament for treating meibomian gland dysfunction in a subject in need thereof. Modes of Administration [0277] In some embodiments, the disclosure provides methods comprising administering an rAAV vector, the rAAV vector comprising an AAV capsid and an expression cassette comprising a polynucleotide encoding TRX operatively linked to a promoter, to the eye of the subject, to a lacrimal gland of the eye of the subject, or to the trabecular meshwork of the eye of a subject. In some embodiments, the disclosure provides methods comprising administering an rAAV vector, the rAAV vector comprising an AAV capsid and an expression cassette comprising a polynucleotide encoding PDI operatively linked to a promoter, to the eye of the subject, to a lacrimal gland of the eye of the subject, or to the trabecular meshwork of the eye of a subject. [0278] As noted above, the lacrimal functional unit is composed of main and accessory lacrimal glands, the ocular surface, and the interconnecting innervation. For each eye, a main lacrimal gland is situated superotemporally in the orbital within the lacrimal fossa of the frontal bone. The accessory glands, known as the Wolfring’s glands and Krause’s glands are located in the eyelid. In the upper eyelid there are about 2 to 5 Wolfring’s glands and about forty Krause’s glands. In the lower eyelid there are about 6 to 8 Krause’s glands. Specific location and anatomy of the lacrimal functional unit is well-known (Conrady et al. J Ophthalmol.; 2016: 7542929 (2016)). Together, the lacrimal glands secrete tear film onto the ocular surface through lacrimal ducts. Lacrimal glands also express and secrete proteins and products necessary for corneal regeneration and promoting transparency into the tear film, such as transforming growth factor-β and retinol (Conrady et al. J Ophthalmol.; 2016: 7542929 (2016); Pan et al. Optom Vis Sci.; 95:27-31 (2018)). In addition to secreting tears into the eye, the lacrimal duct drains the lacrimal fluid into the nasal cavity. [0279] Administration of an rAAV vector to the lacrimal gland may be accomplished by topical administration to the ocular surface, direct injection into the lacrimal gland, and/or topical administration to the lacrimal gland. The lacrimal gland may be accessed surgically or 037525.00573 by manipulation of the eyelid. Manipulation of the eyelid provides access to the tissue for administration topically (e.g. by lavage of the tissue with a pharmaceutical composition comprising the rAAV vector). Direct injection into the lacrimal gland may be done by penetrating the skin over the lacrimal gland (FIG.2A) or by manipulating the eyelid to access the lacrimal gland (FIG.2B). Administration of an rAAV vector to the lacrimal gland may be accomplished by transconjunctival injection. In some embodiments, the rAAV vector is administered to the lacrimal gland by direct injection as depicted in FIG. 2A. In some embodiments, the rAAV vector is administered to the lacrimal gland by manipulating the eyelid as depicted in FIG.2B. [0280] In some embodiments, cells within the eye, the lacrimal gland, and/or the nasolacrimal duct are transduced or transfected by the rAAV vector. Cells within the eye, the lacrimal gland and/or the nasolacrimal duct include, without limitation, acinar cells, ductal cells, and/or myoepithelial cells, as well as cells of the iris and ciliary body (“ICB”), lens epithelial cells, cells of the meibomian glands and the trabecular meshwork. In some embodiments, the transduced or transfected cells within the eye, the lacrimal gland, and/or the nasolacrimal duct express a therapeutically effective amount of TRX. In some embodiments, the transduced or transfected cells in the eye, the lacrimal gland, and/or the nasolacrimal duct secret a therapeutically effective amount of TRX into the tear film. In some embodiments, cells within the meibomian glands are transduced or transfected by the rAAV vector. In some embodiments, cells within the trabecular meshwork are transduced or transfected by the rAAV vector. In some embodiments, a therapeutically effective amount of TRX is secreted into the nasal cavity of the subject. In some embodiments, a therapeutically effective amount of TRX is secreted onto the ocular surface of the subject. [0281] In some embodiments, the transfected or transduced cells within the eye, the lacrimal gland, and/or the nasolacrimal duct express a therapeutically effective amount of PDI. In some embodiments, the transfected or transduced cells in the eye, the lacrimal gland, and/or the nasolacrimal duct secret a therapeutically effective amount of PDI into the tear film. In some embodiments, a therapeutically effective amount of PDI is secreted into the nasal cavity of the subject. In some embodiments, a therapeutically effective amount of PDI is secreted onto the ocular surface of the subject. [0282] Delivery of rAAV vectors to the eye and/or lacrimal gland to express a transgene into tear film has been demonstrated in vivo. The main lacrimal glands of mice were directly injected with rAAV vectors encoding a luciferase transgene with serotypes AAV2, AAV4, 037525.00573 AAV5, AAV 5w8, AAV x5, AAV 9, AAV12, and bovine AAV (BAAV). AAV9, AAV 5w8, AAV5, and AAV2 each are able to transduce the lacrimal ductal and acinar cells of the lacrimal gland (Rocha et al., supra). [0283] In some embodiments, the rAAV vector is administered to a lacrimal gland of the subject. In some embodiments, the lacrimal gland is the main lacrimal gland. In some embodiments, the lacrimal gland is any one of the Wolfring’s glands or the Krause’s glands of the subject. [0284] Compositions and rAAV vectors of the disclosure may be administered to the lacrimal gland of the subject by any suitable method. For example, the subject composition may be administered by direct injection to the main or accessory lacrimal glands. [0285] Access to the lacrimal gland in human subjects can be achieved, for example, by manually elevating the upper eyelid to expose the palpebral lobe of the lacrimal gland and delivering the therapeutic agent using a syringe, e.g., with a 30G needle. [0286] In some embodiments, the rAAV vector is administered to the trabecular meshwork of the eye of a subject. [0287] In some embodiments, the rAAV vector is administered to the endothelial cells of the cornea of a subject. [0288] The rAAV vectors of the disclosure are generally delivered to the subject as a pharmaceutical composition. Pharmaceutical compositions comprise a pharmaceutically acceptable solvent (e.g. water, etc.) and one or more excipients. In some embodiments, the pharmaceutical compositions comprise a buffer at about neutral pH (pH 5, 6, 7, 8, or 9). In some embodiments, the pharmaceutical composition comprises phosphate buffered saline (e.g. PBS at pH of about 7). The pharmaceutical compositions may comprise a pharmaceutically acceptable salt. The concentration of the salt may be selected to ensure that the pharmaceutical composition is isotonic to, or nearly isotonic to, the target tissue. [0289] In various embodiments, the pharmaceutical compositions of the disclosure comprise about 1 × 10 8 genome copies per milliliter (GC/mL), about 5 × 10 8 GC/mL, about 1 × 10 9 GC/mL, about 5 × 10 9 GC/mL, about 1 × 10 10 GC/mL, about 5 × 10 10 GC/mL, about 1 × 10 11 GC/mL, about 5 × 10 11 GC/mL, about 1 × 10 12 GC/mL, about 5 × 10 12 GC/mL, about 5 × 10 13 GC/mL, or about 1 × 10 14 GC/mL of the rAAV vector. In various embodiments, the pharmaceutical compositions of the disclosure comprise about 1 × 10 8 genome copies per milliliter (GC/mL), about 5 × 10 8 GC/mL to about 1 × 10 9 GC/mL, about 1 × 10 9 GC/mL to about 5 × 10 9 GC/mL, about 5 × 10 9 GC/mL to about 1 × 10 10 GC/mL, about 1 × 10 10 GC/mL 037525.00573 to about 5 × 10 10 GC/mL, about 5 × 10 10 GC/mL to about 1 × 10 11 GC/mL, about 1 × 10 11 GC/mL to about 5 × 10 11 GC/mL, about 5 × 10 11 GC/mL to about 1 × 10 12 GC/mL, about 1 × 10 12 GC/mL to about 5 × 10 12 GC/mL, about 5 × 10 12 GC/mL to about 5 × 10 13 GC/mL, or about 5 × 10 13 GC/mL to about 1 × 10 14 GC/mL of the rAAV vector. In various further embodiments, the pharmaceutical compositions of the disclosure comprise about 1 × 10 8 genome copies per milliliter (GC/mL), about 5 × 10 8 GC/mL to about 5 × 10 9 GC/mL, about 5 × 10 9 GC/mL to about 5 × 10 10 GC/mL, about 5 × 10 10 GC/mL to about 5 × 10 11 GC/mL, about 5 × 10 11 GC/mL to about 5 × 10 12 GC/mL, or about 5 × 10 12 GC/mL to about 1 × 10 14 GC/mL of the rAAV vector. In some embodiments, the pharmaceutical compositions of the disclosure comprise about 5 × 10 8 GC/mL to about 5 × 10 10 GC/mL, about 5 × 10 10 GC/mL to about 5 × 10 12 GC/mL, or about 5 × 10 12 GC/mL to about 1 × 10 14 GC/mL of the rAAV vector. [0290] In some the pharmaceutical compositions of the disclosure comprise about 1 × 10 12 GC/mL to about 6.2 × 10 12 GC/mL of the rAAV vector. In some the pharmaceutical compositions of the disclosure comprise about 1 × 10 12 GC/mL or about 6.2 × 10 12 GC/mL of the rAAV vector. [0291] In some embodiments, the pharmaceutical compositions of the disclosure are administered in a total volume of about 10 µL, about 20 µL, about 30 µL, about 40 µL, about 50 µL, about 60 µL, about 70 µL, about 80 µL, about 90 µL, about 100 µL, 110 µL, about 120 µL, about 130 µL, about 140 µL, about 150 µL, about 160 µL, about 170 µL, about 180 µL, about 190 µL, or about 200 µL. In some embodiments, the pharmaceutical compositions of the disclosure are administered in a total volume of about 10 µL to about 20 µL, about 20 µL to about 30 µL, about 30 µL to about 40 µL, about 40 µL to about 50 µL, about 50 µL to about 60 µL, about 60 µL to about 70 µL, about 70 µL to about 80 µL, about 80 µL to about 90 µL, about 90 µL to about 100 µL, about 100 µL to 110 µL, 110 µL to about 120 µL, about 120 µL to about 130 µL, about 130 µL to about 140 µL, about 140 µL to about 150 µL, about 150 µL to about 160 µL, about 160 µL to about 170 µL, about 170 µL to about 180 µL, about 180 µL to about 190 µL, or about 190 µL to about 200 µL. [0292] Genome copies per milliliter can be determined by quantitative polymerase change reaction (qPCR) using a standard curve generated with a reference sample having a known concentration of the polynucleotide genome of the virus. For AAV, the reference sample used is often the transfer plasmid used in generation of the rAAV vector but other reference samples may be used. 037525.00573 [0293] Alternatively or in addition, the concentration of a viral vector can be determined by measuring the titer of the vector on a cell line. Viral titer is typically expressed as viral particles (vp) per unit volume (e.g., vp/mL). In various embodiments, the pharmaceutical compositions of the disclosure comprise about 1 × 10 8 viral particles per milliliter (vp/mL), about 5 × 10 8 vp/mL, about 1 × 10 9 vp/mL, about 5 × 10 9 vp/mL, about 1 × 10 10 vp/mL, about 5 × 10 10 vp/mL, about 1 × 10 11 vp/mL, about 5 × 10 11 vp/mL, about 1 × 10 12 vp/mL, about 5 × 10 12 vp/mL, about 5 × 10 13 vp/mL, or about 1 × 10 14 vp/mL of the rAAV vector. In various further embodiments, the pharmaceutical compositions of the disclosure comprise about 1 × 10 8 viral particles per milliliter (vp/mL) to about 5 × 10 8 vp/mL, about 5 × 10 8 vp/mL to about 1 × 10 9 vp/mL, about 1 × 10 9 vp/mL to about 5 × 10 9 vp/mL, about 5 × 10 9 vp/mL to about 1 × 10 10 vp/mL, about 1 × 10 10 vp/mL to about 5 × 10 10 vp/mL, about 5 × 10 10 vp/mL to about 1 × 10 11 vp/mL, about 1 × 10 11 vp/mL to about 5 × 10 11 vp/mL, about 5 × 10 11 vp/mL to about 1 × 10 12 vp/mL, about 1 × 10 12 vp/mL to about 5 × 10 12 vp/mL, about 5 × 10 12 vp/mL to about 5 × 10 13 vp/mL, or about 5 × 10 13 vp/mL to about 1 × 10 14 vp/mL of the rAAV vector. Assessment of Efficacy [0294] A variety of tests are available to evaluate ocular conditions in a subject before, during, and after treatment with any of the methods or compositions disclosed herein. In some of the embodiments disclosed herein, the effective treatment of the subject is indicated by one or more of the tests that can be, for example, a) Eye Dryness score test on a visual analog scale, b) Schirmer’s test, c) Corneal Fluorescein Staining test, and d) Ocular Surface Disease Index test. In some embodiments, the effective treatment of the subject is indicated by one or more of the tests that can be, for example Symptom Assessment in Dry Eye Questionnaire (SANDE), meibomian gland atrophy/drop-out, expression of glands, meibography/meibometry, tear film lipid layer thickness, corneal fluorescein staining, tear break up time (TBUT), distance- corrected near visual activity (DCNVA), intraocular pressure measurement (e.g., tonometry), visual acuity, slit lamp examination, or ophthalmoscope examination. Tests to evaluate the signs and symptoms of an ocular condition may be administered under standardized or reproducible conditions in order to obtain a subject’s test score. Conditions include exposing the subject to an environment artificially created to adversely challenge the subject or where the environment (temperature, humidity, air flow) is monitored and carefully controlled. [0295] The efficacy of a method described herein can be assessed using any suitable method known in the art. 037525.00573 [0296] In some embodiments, the methods described herein result in one or more symptoms of the ocular condition being reduced compared to the symptoms of the ocular condition before administration of the rAAV vector. As used herein, “symptoms” include any of the diagnostic criteria or symptoms associated with a given ocular condition, including those described herein. Non-limiting examples of symptoms that may be alleviated by treatment in accordance with the methods described herein include, for example, a worsening of visual acuity, as well as the requirement for corrective lenses (e.g., spectacles or contact lenses) and/or surgery. [0297] In some embodiments, a method of treatment described herein results in a delay of the onset of an ocular condition. In some embodiments, the onset of an ocular condition is delayed compared to the onset of the ocular condition in a control subject. In some embodiments, the onset of the ocular condition is delayed compared to the onset of the ocular condition in a contralateral eye. In some embodiments, a method of treatment described herein results in a delay of the progression of an ocular condition. In some embodiments, the progression of an ocular condition is delayed compared to the progression of the ocular condition in a control subject. In some embodiments, the progression of the ocular condition is delayed compared to the progression of the ocular condition in a contralateral eye. A “control subject” may be, for example, an untreated control subject. In some embodiments, the control subject is an age-matched subject who is not treated with an rAAV vector comprising an expression cassette, the expression cassette comprising a polynucleotide encoding TRX or PDI. In some embodiments, a control subject is an age-matched untreated subject. By “contralateral eye” it is meant the eye of the subject that is opposite from the eye that has been treated with a composition according to the present disclosure. The contralateral eye can be used as a control for treatment, so long as the subject suffers from bilateral disease, or in the case of a model animal, has been subjected to the experimental protocol leading up to treatment in both eyes. [0298] A method of treatment described herein may results in the slowing of the progression of an ocular condition. In some embodiments, the progression of the condition in the subject is slowed by about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 705, about 70% to about 80%, about 80% to about 90%, about 90% to about 95% or by more than about 95% compared to a control subject. [0299] In some embodiments, a method of treatment described herein results in the onset of the condition in a subject being delayed by about 6 months to about 9 months, about 9 037525.00573 months to about 12 months, about 12 months to about 15 months, about 15 months to about 18 months, about 18 months to about 21 months, about 21 months to about 24 months, to about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or by more than 20 years compared to a control subject. [0300] In some embodiments, a method of treatment described herein results in an increase in visual acuity in a subject. In some embodiments, a method of treatment described herein results in a delay in the decrease in visual acuity in a subject, e.g., compared to a contralateral eye or compared to a control subject. Visual acuity can be measured using charts on which a subject as to identify letters from a certain distance, including, for example, the Snellen acuity chart, and the Early Treatment of Diabetic retinopathy Study (ETDRS) chart (Bailey and Kitchin, Vision Research 90 (2013) 2–9; Bennet et al., Semin Pediatr Neurol. 2019 October; 31: 30–40). Visual acuity may also be assessed using binocular distance corrected near visual acuity (DCNVA). [0301] In some embodiments, the visual acuity of a subject treated in accordance with a method described herein remains unchanged for at least about 6 months to about 9 months, about 9 months to about 12 months, about 12 months to about 15 months, about 15 months to about 18 months, about 18 months to about 21 months, about 21 months to about 24 months, to about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or for more than 20 years after the administration of the rAAV vector. [0302] In some embodiments, the visual acuity of a subject treated in accordance with a method described herein does not decrease by more than 5% for at least about 6 months to about 9 months, about 9 months to about 12 months, about 12 months to about 15 months, about 15 months to about 18 months, about 18 months to about 21 months, about 21 months to about 24 months, to about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or for more than 20 years after the administration of the rAAV vector. In some embodiments, the visual acuity of a subject treated 037525.00573 in accordance with a method described herein does not decrease by more than 10% for at least about 6 months to about 9 months, about 9 months to about 12 months, about 12 months to about 15 months, about 15 months to about 18 months, about 18 months to about 21 months, about 21 months to about 24 months, to about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or for more than 20 years after the administration of the rAAV vector. [0303] Another indicator of visual acuity may be the requirement for corrective lenses (e.g., contact lenses or spectacles), usually increasing in strength as a condition progresses. In some embodiments, a subject treated in accordance with a method described herein requires corrective lenses prior to the administration of the rAAV vector and the method results in an unchanged requirement for the strength of corrective lenses for at least about 6 months to about 9 months, about 9 months to about 12 months, about 12 months to about 15 months, about 15 months to about 18 months, about 18 months to about 21 months, about 21 months to about 24 months, to about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or for more than 20 years after the administration of the rAAV vector. [0304] A method of treatment described herein may reduce in slowed or delayed cataract formation in a subject, e.g., in comparison to a contralateral eye or in comparison to a control subject. The formation of a cataract can be graded using any method known in the art including, for example, cataract severity grading as defined under the Lens Opacities Classification System III. [0305] In some embodiments, the formation of cataracts in the subject is slowed by about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 705, about 70% to about 80%, about 80% to about 90%, about 90% to about 95% or by more than about 95% compared to a control subject. [0306] In some embodiments, a method of treatment described herein results in the onset of cataract formation in a subject being delayed by about 6 months to about 9 months, about 9 months to about 12 months, about 12 months to about 15 months, about 15 months to about 18 037525.00573 months, about 18 months to about 21 months, about 21 months to about 24 months, to about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or by more than 20 years compared to a control subject. [0307] In some embodiments, a subject treated in accordance with the methods described herein has cataracts prior to the administration of the rAAV vector and the method results in an unchanged grade of cataracts for at least about 6 months to about 9 months, about 9 months to about 12 months, about 12 months to about 15 months, about 15 months to about 18 months, about 18 months to about 21 months, about 21 months to about 24 months, to about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or for more than 20 years after the administration of the rAAV vector. [0308] In some embodiments, the effective treatment of the subject is indicated by a symptom assessment in dry eye questionnaire (SANDE). In some embodiments, the effective treatment of the subject is indicated by meibomian gland atrophy/drop-out. In some embodiments, the effective treatment of the subject is indicated by expression of glands. In some embodiments, the effective treatment of the subject is indicated by meibography/meibometry. In some embodiments, the effective treatment of the subject is indicated by tear film lipid layer thickness. In some embodiments, the effective treatment of the subject is indicated by corneal fluorescein staining, In some embodiments, the effective treatment of the subject is indicated by tear break up time (TBUT). In some embodiments, the effective treatment of the subject is indicated by distance-corrected near visual acuity (DCNVA). In some embodiments, the effective treatment of the subject is indicated by intraocular pressure measurement. In some embodiments, the effective treatment of the subject is indicated by visual acuity. In some embodiments, the effective treatment of the subject is indicated by slit lamp examination. In some embodiments, the effective treatment of the subject is indicated by ophthalmoscope examination. The methods described herein for assessing effective treatment of a subject are known to those of skill in the art. 037525.00573 Maintenance Of Effective Treatment Over Time [0309] The efficacy of a method of treatment described herein may be evaluated at any suitable time point after administration, for example, at about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 18 months, about 24 months, about 3 years, about 4 years or about 5 years after the administration of an rAAV vector described herein. In some embodiments, the efficacy is measured at two or more time points after the administration of an rAAV vector described herein, for example, every 3 months, every 6 months or every 12 months after the administration of the rAAV vector. [0310] The present disclosure may provide for effective treatment over a period of time where a measure of efficacy (e.g., visual acuity) is maintained. The term “maintained” as used in the present disclosure and as it relates to the maintenance of a measure of efficacy (e.g., visual acuity) in a subject’s score refers to the statistically significant improvement not diminishing below a certain threshold over time. The efficacy measure after treatment according to the disclosed methods can be maintained without additional dosing or after one or more subsequent doses. Dosing Timing And Methods Of Administration [0311] The schedule of doses administered to a subject depends on various considerations including the duration of effectiveness of each dose, the transduction (or transfection) efficiency of the rAAV vector, and the effect of the dose on the body. For example, wherein the patient’s condition does not improve, upon the health provider’s discretion, the method of treating an ocular condition as described herein, may be adjusted in dose or administered repeatedly in order to ameliorate or otherwise control or limit the symptoms of the subject’s ocular condition. For instance, the period of time between administrations of one or more doses is extended, or the period of time between days the subject is administered one or more doses is extended. As a non-limiting example, administration of one or more doses is modified to administration of one or more doses after measuring symptoms of the ocular condition. [0312] The term “dose”, as used herein, may refer to a dose of a pharmaceutical composition of the disclosure, or a dose of the treatment that reduces symptoms in an ocular condition. [0313] In some of the embodiments described herein, a dose of the rAAV vector is a dose of a rAAV vector carrying an expression cassette. In such cases, delivery of an appropriate 037525.00573 dose (e.g., effective amount) of the gene product is achieved by administering an appropriate amount/titer of the rAAV vector to the target site which allows expression of an effective amount of the gene product over a period of time. An “effective amount,” as used herein, refers to an amount or dose of an rAAV, treatment, or composition described herein that is sufficient to reduce the symptoms and or signs of an ocular condition described herein. The term “amount” as used herein refers to an absolute amount (e.g., an absolute amount of protein or rAAV particles) or concentration (e.g., a concentration of protein in a solution), whether the amount referred to in a given instance refers to an absolute amount, concentration, or both, will be clear to the skilled artisan based on the context provided herein. [0314] In some embodiments, the rAAV vector is an rAAV virion. In some embodiments, the rAAV vector is administered to the lacrimal gland. In some embodiments, the rAAV vector is administered to the lacrimal gland by topical administration. In some embodiments, the rAAV vector is administered to the lacrimal gland by direct injection. In some embodiments, the rAAV vector is administered to the trabecular meshwork. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for a period of time (e.g., about 1 day, about 2 days, about 4 days, about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 9 months, about 12 months, or longer). In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for about 1 week. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for about 2 weeks. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for about 3 weeks. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for about 4 weeks. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for about 1 month. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for about 2 months. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for about 3 months. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for about 4 months. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for about 5 months. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for about 6 months. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product 037525.00573 for about 9 months. In some embodiments, a dose of the rAAV vector results in the stable production of the gene product for about 12 months. [0315] In some embodiments, a method described herein comprises administering an effective amount of an rAAV vector described herein to a subject, wherein the rAAV vector comprises a polynucleotide encoding at least one gene product (e.g., TRX and/or PDI). In some embodiments, the method comprises delivering a first dose and one or more subsequent doses of the rAAV vector. The one or more subsequent doses are administered after a period of time after the first dose. In some embodiments, this period of time between the first dose and the next subsequent dose is at least 1 day, at least 3 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 1 month, at least 2 months, at least 4 months, at least 6 months, at least 9 months, at least 12 months, or longer. In some embodiments, this period of time between the first dose and the next subsequent dose is between 1-7 days, between 1-4 weeks, between 2-6 weeks, between 4-8 weeks, between 1-3 months, between 2-4 months, between 3-6 months, between 4-12 months, between 6-24 months. In some embodiments, the period of time between the one or more subsequent doses is at least 1 day, at least 3 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 1 month, at least 2 months, at least 4 months, at least 6 months, at least 9 months, at least 12 months, or longer. In some embodiments, the period of time between the one or more subsequent doses is between 1-7 days, between 1-4 weeks, between 2-6 weeks, between 4-8 weeks, between 1-3 months, between 2-4 months, between 3-6 months, between 4-12 months, between 6-24 months. [0316] In some embodiments, the method comprises a first dose and one or more subsequent doses of the rAAV vector. In some embodiments, the one or more subsequent doses are administered after a period of time after the first dose. This period of time between the first dose and the next subsequent dose is at least 1 hour, at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours, at least 6 hours, at least 7 hours, or at least 8 hours. The period of time between the first dose and the next subsequent dose is between 1-3 hours, 2-4 hours, 3-6 hours, or 4-8 hours. The period of time between the one or more subsequent doses is at least 1 hour, at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours, at least 6 hours, at least 7 hours, or at least 8 hours. The period of time between the one or more subsequent doses is between 1-3 hours, 2-4 hours, 3-6 hours, or 4-8 hours. 037525.00573 Pharmaceutical Compositions and Kits [0317] In some embodiments, the disclosure provides a pharmaceutical composition comprising an rAAV vector described herein. In some embodiments, the pharmaceutical composition comprises an rAAV vector described herein, and a pharmaceutically acceptable carrier, delivery agent, or excipient. [0318] In some embodiments, the disclosure provides use of an rAAV vector or pharmaceutical composition described herein, in the manufacture of a medicament for treatment of an ocular disease, disorder, or condition. In some embodiments, the disclosure provides use of an rAAV vector or pharmaceutical composition herein for use, or adaptable for use, in the treatment of an ocular disease, disorder, or condition. [0319] In some embodiments, the pharmaceutically acceptable carrier comprises phosphate buffered saline. In some embodiments, the pharmaceutical composition is formulated to be compatible with its intended route of administration (e.g., intralacrimal). In some embodiments, the pharmaceutical composition is formulated for administration into the lacrimal gland. In some embodiments, the pharmaceutical composition is formulated for administration onto the ocular surface. [0320] In some embodiments, the disclosure provides a pharmaceutical composition for use in treating an ocular condition in a subject, wherein the pharmaceutical composition comprises a vector, such as any rAAV vector as described herein, encoding an oxidoreductase as described herein and a pharmaceutically acceptable carrier. Any concentration of the rAAV vector that is suitable to effectively transduce or transfect cells of the eye, the lacrimal gland, the meibomian glands, and/or the trabecular meshwork cells can be prepared for contacting cells of the eye, the lacrimal gland, the meibomian glands, and/or the trabecular meshwork in vitro or in vivo. For example, the rAAV may be formulated at a concentration of 10 8 vector genomes per ml or more, for example, 5×10 8 vector genomes per mL; 10 9 vector genomes per mL; 5×10 9 vector genomes per mL, 10 10 vector genomes per mL, 5×10 10 vector genomes per mL; 10 11 vector genomes per mL; 5×10 11 vector genomes per mL; 10 12 vector genomes per mL; 5×10 12 vector genomes per mL; 10 13 vector genomes per mL; 1.5×10 13 vector genomes per mL; 3×10 13 vector genomes per mL; 5×10 13 vector genomes per mL; 7.5×10 13 vector genomes per mL; 9×10 13 vector genomes per mL; 1×10 14 vector genomes per mL, 5×10 14 vector genomes per mL or more, but typically not more than 1×10 15 vector genomes per mL Similarly, any total number of rAAV vectors suitable to provide appropriate transduction or 037525.00573 transfection of cells of the eye, the lacrimal gland, the meibomian glands, and/or the trabecular meshwork cells to confer the desired effect or treat the disease can be administered to the mammal or to the primate’s eye. In various preferred embodiments, at least 10 5 ; 2.5x10 5 ; 5x10 5 ; 7.5x10 5 ; 10 6 ; 2.5x10 6 ; 5x10 6 ; 7.5x10 6 ; 10 7 ; 2.5×10 7 ; 5x10 7 ; 7.5×10 7 ; 10 8 ; 2.5×10 8 ; 5×10 8 ; 7.5×10 8 ; 10 9 ; 2.5×10 9 ; 5×10 9 ; 7.5×10 9 ; 10 10 ; 2.5×10 10 ; 5×10 10 ; 7.5×10 10 ; 10 11 ; 2.5×10 11 ; 5×10 11 ; 7.5×10 11 ; 10 12 ; 2.5×10 12 ; 5×10 12 ; 7.5×10 12 ; 10 13 ; 2.5×10 13 ; 5×10 13 ; 7.5×10 13 ; 10 14 , 2.5×10 14 ; 5×10 14 ; 7.5×10 14 ; 10 15 ; 2.5×10 15 ; 5x10 15 ; or 7.5×10 15 ; 10 16 ; 2.5×10 16 ; 5x10 16 ; or 7.5×10 16 rAAV vectors, or more, but typically not more than 1×10 15 rAAv vectors are injected per eye. For example, in some embodiments, about 1 x 10 9 to about 1 x 10 10 , about 1 x 10 10 to about 1 x 10 11 , about 1 x 10 11 to about 1 x 10 12 , about 1 x 10 12 to about 1 x 10 13 , or about 1 x 10 13 to about 1 x 10 15 genome copies of the rAAV vector are administered per eye. In some aspects, the total number of rAAV vectors administered to the eye of the human subject or animal being treated may comprise a concentration within a range defined by any pair of concentrations described in this paragraph. Any suitable number of administrations of the rAAV vectors to the mammal or the primate eye can be made. In some embodiments, the methods comprise a single administration; in other embodiments, multiple administrations are made over time as deemed appropriate by an attending clinician. [0321] In some embodiments, a suitable amount or concentration of rAAV vector (or any other TRX and/or PDI expression construct described herein) in a therapeutic formulation may be a concentration effective to express from 100 pg/mL to 50 µg/mL of TRX and/or of PDI in a tear film of a subject subsequent to administration of the composition to the subject. For example, the amount or concentration of the rAAV vector may be one that results in the expression of 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 µg/mL of TRX and/or of PDI (or a concentration within a range defined by any pair of the foregoing values) in a tear film of a subject. Expression may be measured, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 hours after administration, or after a longer duration of time, such as after 1, 2, 3, 4, or 5 days. [0322] The rAAV vector may be formulated into any suitable unit dosage, including, without limitation, 1×10 8 vector genomes or more, for example, 1×10 9 , 1×10 10 , 1×10 11 , 1×10 12 , or 1×10 13 vector genomes or more, in certain instances, 1×10 14 vector genomes, but usually no more than 4×10 15 vector genomes. In some embodiments, the viral vector is formulated into 037525.00573 any suitable unit dosage, including, without limitation, 1x10 7 , 1×10 8 , 1×10 9 , 1×10 10 , 1×10 11 , 1×10 12 , or 1×10 13 vector genomes or more. In some embodiments, the unit dosage is at most about 5×10 15 vector genomes, e.g., 1×10 14 vector genomes or less, for example 1×10 13 , 1×10 12 , 1×10 11 , 1×10 10 , or 1×10 9 vector genomes or less, in certain instances 1×10 8 vector genomes or less, and typically no less than 1×10 8 vector genomes. In some embodiments, the unit dosage is 1×10 10 to 1×10 11 vector genomes. In some cases, the unit dosage is 1×10 10 to 3×10 12 vector genomes. In some embodiments, the unit dosage is 1×10 9 to 3×10 13 vector genomes. In some embodiments, the unit dosage is 1×10 8 to 3×10 14 vector genomes. In some embodiments, the rAAV vector comprises an AAV capsid and an expression cassette configured to express TRX and/or PDI and a unit dosage is formulated at a concentration of at least, at most, exactly, or about 1x10 5 , 1x10 6 , 1x10 7 , 1×10 8 , 1×10 9 , 1×10 10 , 1×10 11 , 1×10 12 , 1×10 13 , 1×10 14 , 1×10 15 , or 1x10 16 of the rAAV vector, or at a concentration within a range defined by any pair of concentrations described in this paragraph. [0323] In some embodiments, the disclosure provides a vector comprising a plasmid configured to express TRX and/or PDI, and a unit dosage is formulated at a concentration of at least, at most, exactly, or about 1x10 7 , 1×10 8 , 1×10 9 , 1×10 10 , 1×10 11 , 1×10 12 , 1×10 13 , 1×10 14 , or 1×10 15 of the plasmid. [0324] In some embodiments, the unit dosage of pharmaceutical composition may be measured using multiplicity of infection (MOI). By MOI it is meant the ratio, or multiple, of vector or viral genomes of the rAAV vectors provided herein to the cells to which the nucleic acid may be delivered. In some embodiments, the MOI may be 1×10 6 . In some embodiments, the MOI may be 1×10 5 -1×10 7 . In some cases, the MOI may be 1×10 4 -1×10 8 . In some embodiments, recombinant viruses of the disclosure are at least about 1×10 1 , 1×10 2 , 1×10 3 , 1×10 4 , 1×10 5 , 1×10 6 , 1×10 7 , 1×10 8 , 1×10 9 , 1×10 10 , 1×10 11 , 1×10 12 , 1×10 13 , 1×10 14 , 1×10 15 , 1×10 16 , 1×10 17 , and 1×10 18 MOI. In some embodiments, recombinant viruses of this disclosure are 1×10 8 to 3×10 14 MOI. In some embodiments, recombinant viruses of the disclosure are at most about 1×10 1 , 1×10 2 , 1×10 3 , 1×10 4 , 1×10 5 , 1×10 6 , 1×10 7 , 1×10 8 , 1×10 9 , 1×10 10 , 1×10 11 , 1×10 12 , 1×10 13 , 1×10 14 , 1×10 15 , 1×10 16 , 1×10 17 , and 1×10 18 MOI. [0325] In some embodiments, the amount of pharmaceutical composition comprises about 1x10 8 to about 1x10 15 rAAV vectors, about 1x10 9 to about 1x10 14 rAAV vectors, about 1x10 10 to about 1x10 13 rAAV vectors, or about 1x10 11 to about 3x10 12 rAAV vectors. [0326] In preparing the subject rAAV compositions, any host cells for producing rAAV vectors may be employed, including, for example, mammalian cells (e.g.293 cells), insect cells 037525.00573 (e.g. SF9 cells), microorganisms and yeast. Host cells can also be packaging cells in which the AAV rep and cap genes are stably maintained in the host cell or producer cells in which the rAAV vector genome is stably maintained and packaged. Exemplary packaging and producer cells are derived from SF-9, 293, A549 or HeLa cells. rAAV vectors are purified and formulated using standard techniques known in the art. [0327] In some embodiments, the disclosure provides for use of an rAAV vector described herein in the manufacture of a medicament. In some embodiments, the disclosure provides for use of an rAAV vector described herein in the manufacture of a medicament for use in a method described herein. [0328] In some embodiments, the disclosure provides a kit comprising an rAAV herein, and instructions for use. In some embodiments, the kit comprises an rAAV herein, and a package insert containing instructions for use of the kit. In some embodiments, the kit comprises an rAAV herein, and a pharmaceutically acceptable carrier, or a pharmaceutical composition comprising the rAAV and instructions for treating or delaying progression of a disease, disorder, or condition described herein in a subject in need thereof. EXEMPLARY EMBODIMENTS [0329] Embodiments I-1. A recombinant adeno-associated virus (rAAV) vector comprising an AAV capsid and an expression cassette, the expression cassette comprising a polynucleotide encoding an oxidoreductase enzyme, operatively linked to a promoter. [0330] Embodiments I-2. The rAAV vector of embodiment I-1, wherein the oxidoreductase enzyme is thioredoxin (TRX). [0331] Embodiments I-3. The rAAV vector of embodiment I-1, wherein the oxidoreductase enzyme is protein disulfide isomerase (PDI). [0332] Embodiments I-4. The rAAV vector of embodiment I-3, wherein the polynucleotide comprises a sequence encoding a protein that is at least 95% identical to SEQ ID NO: 26. [0333] Embodiments I-5. The rAAV vector of embodiment I-2, wherein the polynucleotide comprises a sequence encoding a protein that is at least 95% identical to SEQ ID NO: 25. [0334] Embodiments I-6. The rAAV vector of embodiment I-2 or I-5, wherein the polynucleotide comprises a sequence that is at least 95% identical to SEQ ID NO: 2. 037525.00573 [0335] Embodiments I-7. The rAAV vector of embodiment I-3 or I-4, wherein the polynucleotide comprises a sequence that is at least 95% identical to SEQ ID NO: 30. [0336] Embodiments I-8. The rAAV vector of any one of embodiments I-1 to I-7, wherein the promoter is a CMV promoter comprising the nucleotide sequence set forth in SEQ ID NO: 17. [0337] Embodiments I-9. The rAAV vector of any one of embodiment I-8, wherein the expression cassette comprises the CMV promoter and a CMV enhancer. [0338] Embodiments I-10. The rAAV vector of any one of embodiments I-1 to I-9, wherein the expression cassette comprises a polyadenylation (polyA) sequence. [0339] Embodiments I-11. The rAAV vector of embodiment I-10, wherein the polyA sequence is a BGH polyA sequence. [0340] Embodiments I-12. The rAAV vector of any one of embodiments I-1 to I-11, wherein the expression cassette comprises a Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE). [0341] Embodiments I-13. The rAAV vector of any one of embodiments I-1 to I-12, wherein the expression cassette comprises a Kozak sequence. [0342] Embodiments I-14. A composition comprising an rAAV vector, wherein the rAAV vector comprises: [0343] (a) an AAV capsid, and [0344] (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 2, and wherein the polynucleotide is linked to a promoter. [0345] Embodiments I-15. The rAAV vector of any one of embodiments I-1 to I-11, wherein the expression cassette is flanked by two inverted terminal repeats (ITRs). [0346] Embodiments I-16. The rAAV vector of embodiment I-12, wherein the ITRs are AAV2 ITRs. [0347] Embodiments I-17. The rAAV vector of any one of embodiments I-1 to I-2, and I- 5 to I-13 or the composition of any one of embodiments I-14 to I-16, wherein the expression cassette comprises a nucleotide sequence that shares at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 16. [0348] Embodiments I-18. The rAAV vector of any one of embodiments I-1 to I-17, wherein the AAV capsid comprises a VP3 that shares at least 95%, 98%, or 100% identity with 037525.00573 AAV2 VP3 (SEQ ID NO: 8), AAV5 VP3 (SEQ ID NO: 10), AAV8 VP3 (SEQ ID NO: 12), or AAV9 VP3 (SEQ ID NO:14). [0349] Embodiments I-19. The rAAV vector of any one of embodiments I-1 to I-17 wherein the AAV capsid comprises a VP3 that shares at least 95%, 98%, or 100% identity with AAV9 (SEQ ID NO: 14). [0350] Embodiments I-20. A composition comprising an rAAV vector, wherein the rAAV vector comprises: [0351] (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and [0352] (b) an expression cassette, wherein the expression cassette comprises a polynucleotide comprising a nucleotide sequence sharing at least 95% identity to a nucleotide sequence comprising SEQ ID NO: 2, and wherein the polynucleotide is linked to a promoter. [0353] Embodiments I-21. A composition comprising an rAAV vector, wherein the rAAV vector comprises: [0354] (a) an AAV2, AAV5, AAV8, or AAV9 capsid, and [0355] (b) an expression cassette, wherein the expression cassette comprises a polynucleotide sequence sharing at least 95% identity to SEQ ID NO: 2. [0356] Embodiments I-22. The composition of embodiment I-20 or I-21, wherein the AAV capsid is AAV2. [0357] Embodiments I-23. The composition of embodiment I-20 or I-21, wherein the AAV capsid is AAV5. [0358] Embodiments I-24. The composition of embodiment I-20 or I-21, wherein the AAV capsid is AAV9. [0359] Embodiments I-25. The rAAV vector or the composition of any one of embodiments I-1 to I-24, wherein the polynucleotide comprises a sequence encoding a signal peptide. [0360] Embodiments I-26. A pharmaceutical composition comprising the rAAV vector or composition of any one of embodiments I-1 to I-25, and a pharmaceutically acceptable carrier. [0361] Embodiments I-27. The pharmaceutical composition of embodiment I-26, wherein the composition comprises about 1 x 10 7 to about 1 x 10 14 genome copies per milliliter of the rAAV vector. [0362] Embodiments I-28. The pharmaceutical composition of embodiment I-26, wherein the composition comprises about 1 x 10 12 to about 6.2 x 10 12 genome copies per milliliter of the rAAV vector. 037525.00573 [0363] Embodiments I-29. A method of treating an ocular condition in a subject in need thereof, the method comprising administering a therapeutically effective amount of the pharmaceutical composition of any one of embodiments I-26 to I-28 to the eye of the subject. [0364] Embodiments I-30. The method of embodiment I-29, wherein the pharmaceutical composition is delivered to an ocular secretory gland of the subject. [0365] Embodiments I-31. The method of embodiment I-29 or I-30, wherein the pharmaceutical composition is delivered to the lacrimal gland. [0366] Embodiments I-32. The method of any one of embodiments I-29 to I-31, wherein the pharmaceutical composition is delivered to an accessory lacrimal gland. [0367] Embodiments I-33. The method of embodiment I-32, wherein the accessory lacrimal gland is the meibomian glands. [0368] Embodiments I-34. The method of any one of embodiments I-29 to I-33, wherein the pharmaceutical composition is delivered to the trabecular meshwork. [0369] Embodiments I-35. The method of any one of embodiments I-29 to I-34, wherein about 1 x 10 9 to about 1 x 10 10 , about 1 x 10 10 to about 1 x 10 11 , about 1 x 10 11 to about 1 x 10 12 , about 1 x 10 12 to about 1 x 10 13 , or about 1 x 10 13 to about 1 x 10 15 genome copies of the rAAV vector are administered. [0370] Embodiments I-36. The method of any one of embodiments I-29 to I-35, wherein the ocular condition is associated with increased oxidative stress. [0371] Embodiments I-37. The method of any one of embodiments I-29 to I-35, wherein the ocular condition is associated with loss of expression and/or function of one or more oxidoreductase enzymes. [0372] Embodiments I-38. The method of any one of embodiments I-29 to I-35, wherein the ocular condition is associated with loss of TRX expression and/or function. [0373] Embodiments I-39. The method of any one of embodiments I-29 to I-35, wherein the ocular condition is associated with loss of PDI expression and/or function. [0374] Embodiments I-40. The method of any one of embodiments I-29 to I-35, wherein the ocular condition is characterized by a loss of near vision. [0375] Embodiments I-41. The method of any one of embodiments I-29 to I-40, wherein the ocular condition is presbyopia. [0376] Embodiments I-42. The method of any one of embodiments I-29 to I-40, wherein the ocular condition is cataract formation. 037525.00573 [0377] Embodiments I-43. The method of any one of embodiments I-29 to I-40, wherein the ocular condition is ocular hypertension. [0378] Embodiments I-44. The method of any one of embodiments I-29 to I-40, wherein the ocular condition is meibomian gland dysfunction (MDI). [0379] Embodiments I-45. The method of any one of embodiments I-29 to I-40, wherein the ocular condition is glaucoma. [0380] Embodiments I-46. The method of any one of embodiments I-29 to I-45, wherein the method results in expression of the oxidoreductase enzyme in the cells of the lacrimal gland and/or an accessory lacrimal gland, and/or in the trabecular meshwork. [0381] Embodiments I-47. The method of any one of embodiments I-29 to I-46, wherein the method results in expression of TRX in the cells of the lacrimal gland and/or an accessory lacrimal gland, and/or in the trabecular meshwork. [0382] Embodiments I-48. The method of any one of embodiments I-29 to I-47, wherein the method results in secretion of TRX into the tear film and/or onto the ocular surface of the subject. [0383] Embodiments I-49. The method of any one of embodiments I-29 to I-48, wherein the method results in an improvement of one or more symptoms of the ocular condition. [0384] Embodiments I-50. The method of anyone of embodiments I-29 to I-49, wherein the method results in an improvement of visual acuity. [0385] Embodiments I-51. The method of any one of embodiments I-29 to I-50, wherein the method results in a reduced need for corrective lenses. [0386] Embodiments I-52. The method of any one of embodiments I-29 to I-51, wherein the method results in a delay of the progression of the condition. [0387] Embodiments I-53. The method of embodiment I-52, wherein the method results in the progression of the condition in the subject being delayed by about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to about 80%, about 80% to about 90%, about 90% to about 95% or by more than about 95% compared to a control subject. [0388] Embodiments I-54. The method of any one of embodiment I-29 to I-53, wherein the method results in the onset of the condition being delayed by about 6 months to about 12 months, about 12 months to about 18 months, about 18 months to about 24 months, about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 037525.00573 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or by more than 20 years compared to a control subject. [0389] Embodiments I-55. The method of embodiment I-53 or I-54, wherein the control subject is an age-matched subject who is not treated with an rAAV vector comprising an expression cassette, the expression cassette comprising a polynucleotide encoding TRX. [0390] Embodiments I-56. The method of any one of embodiments I-29 to I-55, wherein the subject requires corrective lenses prior to the administration of the rAAV, and the administration results in an unchanged requirement for the strength of the corrective lenses for at least about 6 months to about 12 months, about 12 months to about 18 months, about 18 months to about 24 months, about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or for more than 20 years after administration of the rAAV. [0391] Embodiments I-57. The method of any one of embodiments I-29 to I-56, wherein the visual acuity of the subject remains unchanged for at least about 6 months to about 9 months, about 9 months to about 12 months, about 12 months to about 15 months, about 15 months to about 18 months, about 18 months to about 21 months, about 21 months to about 24 months, to about 2 years to about 3 years, about 3 years to about 4 years, about 4 years to about 5 years, about 5 years to about 6 years, about 6 years to about 7 years, about 7 years to about 8 years, about 8 years to about 9 years, about 9 years to about 10 years, about 10 years to about 15 years, about 15 years to about 20 years, or for more than 20 years after the administration of the rAAV vector [0392] Embodiments I-58. The method of any one of embodiments I-29 to I-57, wherein the method further comprises administering one or more additional therapeutic agents. [0393] Embodiments I-59. The method of any one of embodiments I-29 to I-58, wherein the subject is human. [0394] Embodiments I-60. The pharmaceutical composition of any one of embodiments I-26 to I-28 for use in a method of treating an ocular condition in a subject in need thereof comprising administering an effective amount of the pharmaceutical composition to the eye of the subject. 037525.00573 [0395] Embodiments I-61. The pharmaceutical composition of any one of embodiments I-26 to I-28 for use in the manufacture of a medicament for treating an ocular condition in a subject in need thereof. [0396] Embodiments I-62. A compound for use in treating an ocular condition in a subject, comprising administering the composition or rAAV of any one of embodiments I-1 to I-25 or the pharmaceutical composition of rAAV vector of any one of embodiments I-26 to I-28, and a pharmaceutically acceptable carrier. [0397] Embodiments I-63. A kit comprising an rAAV vector or composition of any one of embodiments I-1 to I-25 or the pharmaceutical composition of any one of embodiments I- 26 to I-28, and a pharmaceutically acceptable carrier, and instructions for use in treating an ocular condition in a subject, comprising administering the pharmaceutical composition to the eye of the subject. [0398] Embodiments I-64. A kit comprising an rAAV vector or composition of any one of embodiments I-1 to I-25 or the pharmaceutical composition of any one of embodiments I- 26 to I-28, and a pharmaceutically acceptable carrier, and instructions for use in treating presbyopia in a subject, comprising administering the pharmaceutical composition to the eye of the subject. [0399] Embodiments I-65. A kit comprising an rAAV vector or composition of any one of embodiments I-1 to I-25 or the pharmaceutical composition of any one of embodiments I- 26 to I-28, and a pharmaceutically acceptable carrier, and instructions for use in treating cataract formation in a subject, comprising administering the pharmaceutical composition to the eye of the subject. [0400] Embodiments I-66. A kit comprising an rAAV vector or composition of any one of embodiments I-1 to I-25 or the pharmaceutical composition of any one of embodiments I- 26 to I-28, and a pharmaceutically acceptable carrier, and instructions for use in treating loss of accommodation in a subject, comprising administering the pharmaceutical composition to the eye of the subject. [0401] Embodiments I-67. A kit comprising an rAAV vector or composition of any one of embodiments I-1 to I-25 or the pharmaceutical composition of any one of embodiments I- 26 to I-28, and a pharmaceutically acceptable carrier, and instructions for use in treating ocular hypertension in a subject, comprising administering the pharmaceutical composition to the eye of the subject. 037525.00573 [0402] Embodiments I-68. A kit comprising an rAAV vector or composition of any one of embodiments I-1 to I-25 or the pharmaceutical composition of any one of embodiments I- 26 to I-28, and a pharmaceutically acceptable carrier, and instructions for use in treating meibomian gland dysfunction (MGD) in a subject, comprising administering the pharmaceutical composition to the eye of the subject. [0403] Embodiment I-69. The method of any one of embodiments I-29 to I-59, further comprising administering one or more additional therapeutic agents to the subject. [0404] Embodiment I-70. The method of embodiment I-69, wherein the one or more additional therapeutic agents increases tear production. [0405] Embodiment I-71. The method of embodiment I-70, wherein the one or more additional therapeutic agents that increase tear production is administered via local nasal administration. [0406] Embodiment I-72. The method of embodiment I-71, wherein the local nasal administration is via an intranasal spray. [0407] Embodiment I-73. The method of any one of embodiments I-70 to I-72, wherein the one or more additional therapeutic agents that increase tear production comprises a nicotinic acetylcholine receptor (nAChR) agonist, or a pharmaceutically acceptable salt thereof. [0408] Embodiment I-74. The method of embodiment I-73, wherein the nAChR agonist is a full agonist of a nAChR subtypes selected from alpha4beta2, alpha3beta4, alpha3alpha5beta4, alpha4alpha6beta2, and a combination thereof. [0409] Embodiment I-75. The method of embodiment I-73 or I-74, wherein the nAChR agonist is varenicline, or a pharmaceutically acceptable salt thereof. [0410] Embodiment I-76. The method of embodiment I-73 or I-74, the nAChR agonist is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof. [0411] Embodiment I-77. The method of any one of embodiments I-70 to I-76, wherein the one or more additional therapeutic agents that increases tear production is administered prior to or following the administering of the pharmaceutical composition. [0412] Embodiment I-78. The method of embodiment I-70 to I-77, wherein the one or more additional therapeutic agents that increases tear production is administered at about 1 week following the administering of the pharmaceutical composition. [0413] Embodiment I-79. The method of any one of embodiment I-70 to I-78, resulting in expression of TRX in the tear film and/or cornea of the subject following administration of the pharmaceutical composition. 037525.00573 [0414] Embodiment I-80. The method of embodiment I-79, wherein the expression of TRX in the tear film and/or cornea is increased in a predetermined amount of time compared to an administration of the pharmaceutical composition without the one or more additional therapeutic agents that increases tear production. [0415] Embodiment I-81. The method of embodiment I-80, wherein the predetermined amount of time is about 5 minutes. [0416] Embodiment I-82. The method of embodiment I-80, wherein the predetermined amount of time is about 1 hour. [0417] Embodiment I-83. The method of any one of embodiments I-29 to I-82, wherein the subject is human. EXAMPLES [0418] The following specific examples are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. Example 1A: Expression of Thioredoxin [0419] Expression of Thioredoxin (TRX) in cells transfected with an rAAV vector comprising an expression cassette comprising a transgene encoding TRX (as depicted in FIG. 1 and the sequence of which is SEQ ID NO: 16) was determined by ELISA. The AAV transfer plasmid contained a 5ʹ and 3ʹ AAV2 ITR (SEQ ID NOs: 22 and 23 respectively). Between the 5ʹ and 3ʹ ITR was a cDNA encoding a human TRX polypeptide and cDNA for elements to provide an optimal expression level of TRX polypeptide. The encoded human TRX polypeptide has the amino acid sequence set forth in SEQ ID NO: 1. The cDNA encoding the human TRX polypeptide was codon optimized for improved expression in human cells and has the nucleotide sequence set forth in SEQ ID NO: 2. The nucleotide sequence from 5ʹITR to 3ʹITR is set forth in SEQ ID NO: 16. Table 6 shows the results of the ELISA on a standard curve as well as on samples taken from two separate cell lines in triplicate. Table 6: Expression of TRX 037525.00573 [0420] Next, expression of the AAV-Thioredoxin plasmid in 293T cells was evaluated. 293T cells were plated in 6 well plates at 6.5 x10 5 cells per well and transfected with 2.5 µg of AAV.TRX plasmid DNA utilizing Lipofectamine 3000 per the manufacturer’s protocol. The cells were grown out and then plated at 5.5x10 5 on 35 mm glass bottom tissue culture plates. Twenty-four hours post-transfection with no media changes transfected and non-transfected cells were stained with a primary polyclonal antibody to thioredoxin (immunogen: MVKQIESKTAFQEALDAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEV DVDDCQDVASECEVKCMPTFQFFKKGQKVGEFSGANKEKLEATINELV; SEQ ID NO: 1) and an AlexaFluor 488 fluorescently-tagged secondary antibody. The cells were counterstained with 4′,6-diamidino-2-phenylindole (DAPI) and then imaged on a fluorescent microscope at 20 and 40x magnification. The results shown in FIG. 4 demonstrate the expression of thioredoxin protein indicated by the bright and punctate signal present in the AAV-Thioredoxin transfected cells as compared to minimal signal in the non-transfected control cells.293T cells do express some level of thioredoxin albeit at a lesser amount than the AAV.TRX plasmid transfected cells as shown in FIG.4. [0421] Given the endogenous expression of thioredoxin in 293T cells, a study was conducted with 4 biological replicates to compare the expressed and secreted levels of thioredoxin in non-transfected 293T cells and the AAV.TRX plasmid DNA transfected cells. Cells were cultured and media was collected. ELISA results for non-transfected and transfected 293T cells are show in FIGs.5A-5B respectively. It should be noted that the non-transfected cell conditioned media was collected 4 days after transfection to allow adequate accumulation of thioredoxin for detection in an ELISA; whereas, the AAV.TRX transfected cell conditioned media was collected just 24 hours after transfection. Additionally, the y-axes in FIGs.5A-5B are markedly different given the amount of expression. The non-transfected cells expressed and secreted thioredoxin to a mean concentration of 19.86 nanogram/mL in conditioned media and AAV.TRX transfected cells levels were 14.3 µg/mL. Thioredoxin standard curves generated (data not shown) for the ELISA analyses of undiluted and diluted conditioned media had R 2 values of 0.999. 037525.00573 [0422] Western blot analysis was conducted on 293T cells and 293T cells transfected with AAV.TRX. Whole cell extracts were run on a western blot 48 hours following transfection and a western blot for thioredoxin and GAPDH (FIG. 6) were conducted to assess thioredoxin protein levels in whole cell extracts with a GAPDH protein loading control for comparison of endogenous and AAV.TRX driven thioredoxin protein expression. SDS-PAGE was run with 30µg of protein per lane and a polyclonal primary antibody to thioredoxin was utilized with a secondary anti-rabbit IgG antibody with a horseradish peroxidase (HRP) tag for the anti- thioredoxin western blot. Additionally, a loading control western blot utilizing an antibody to GAPDH was also run to standardize protein loading. Band densitometry analysis was performed with Image J software developed by the National Institute of Health. The AAV.TRX plasmid DNA transfected whole cell extracts produced 3.5 times more thioredoxin than the non-transfected 293T cells based upon densitometry analysis. Example 1B: Expression of Thioredoxin, Additional Studies [0423] A second western blot analysis was conducted with an anti-thioredoxin primary antibody (ThermoFisher Catalog #14999-1-AP) and an anti-rabbit IgG HRP secondary antibody (ProMega Catalog #A5316). The results are shown in FIG. 13 and demonstrate the presence of the thioredoxin transgene product at 2, 4 and 6 hours in transfected 293T cells, but not present in non-transfected cells. Additionally, whole cell extracts were collected 24 hours following transfection and western blot analysis was performed using an actin loading control. The transfected cells (AAV.TXN) demonstrate a significant amount of protein detected with the anti-thioredoxin primary antibody at the relevant molecular weight demonstrated in FIG. 14. [0424] To assess the functional activity of the expressed transgene product, a thioredoxin activity assay (Cayman Chemical Thioredoxin Fluorometric Activity Assay Catalog #500228) was conducted on conditioned media and whole cell lysates of transfected cells using non- transfected cells as a control. The principle of the assay is to assess the ability of the transgene product to reduce a disulfide bond. This is achieved by a substrate consisting of insulin with a disulfide bond linking it to eosin. The reduction of this disulfide bond releases the eosin from the insulin, which can be detected at a wavelength of 560 nm. An increase in thioredoxin activity is directly proportional to the rate of increase of fluorescence (i.e., eosin releasing from 037525.00573 the insulin-eosin substrate). The thioredoxin activity is calculated per the manufacturer’s recommendation using the following equation: [0425] For this assay, 293T cells were transfected with AAV-TXN and 18 hours later washed and media was replaced with OPTImem cell culture media. Media was collected 6 hours after replenishment to conduct the assay and readings were collected every 60 seconds for 60 minutes and recombinant thioredoxin served as a positive control and eosin was used to generate a standard curve of fluorescence at 560 nm. FIG.15 demonstrates that the thioredoxin transgene product expressed and secreted into conditioned media is active and able to reduce the disulfide bond of the eosin-labeled insulin substrate. The recombinant thioredoxin (Recombinant Trx) positive control was loaded into the assay at 120 ng/well and had a thioredoxin activity of 62.45 nM/minute. The 293T cells transfected with the thioredoxin transgene plasmid exhibited thioredoxin activity of 56.8 nm/minute and the non-transfected 293T cells demonstrated an endogenous thioredoxin activity level of 16.90 nM/minute. This functional assay confirms the expression, secretion and function of the transgene product from the construct depicted in FIG. 1 and demonstrates the ability of the expressed thioredoxin transgene product to reduce disulfide bonds after secretion from a target cell. This finding supports the ability of the transgene product to diffuse from the cells expressing the transgene with the ability to reduce disulfide bonds formed from oxidative stress. Example 2: Intra-Lacrimal Gland Gene Therapy using rAAV vector [0426] This example shows a 9-day pilot study of single dose rAAV vectors administered as an intra-lacrimal gland injection followed by a single dose of varenicline administered as an intranasal dose to Dutch-Belted rabbits. It evaluates the effectiveness and tolerability of a panel of rAAV vector embodiments administered one time via injection to the lacrimal gland. Each rAAV vector composition in the panel is tested at two concentrations (1×10 12 GC/mL and 6.2×10 12 GC/mL). The panel of rAAV vectors include embodiments with capsid proteins having AAV2, AAV5, AAV8, and AAV9 serotypes. The expression cassette delivered by the rAAV vector encoded an enhanced green fluorescent protein (eGFP) transgene that is operatively linked to a CMV promoter (FIG. 7). On day 9 following injection of the rAAV vector, the animal is given an intranasal dose of varenicline. The varenicline induces tear 037525.00573 production in the animals such that eGFP delivered to the lacrimal by the rAAV vector and expressed under control of the CMV promoter in cells of the lacrimal gland will be secreted into the tear film and onto the ocular surface of the animal. Two main objectives will be achieved using this approach: (1) Test the feasibility of capsid protein serotypes AAV2, AAV5, AAV8, and AAV9 to deliver a transgene to cells in the lacrimal gland resulting in measurable CMV promoter-driven expression of the transgene within the cells; and (2) Assess the feasibility of increasing the relative amount of the transgene encoded by the expression cassette into the tear film and onto the ocular surface of the animal. [0427] Animal studies were carried out in the Charles River Laboratories (CRL) facilities by CRL staff scientific personnel. Animal Test System, Husbandry, and In-life Monitoring [0428] The animals used in this study were male Dutch-Belted rabbits between the ages of 4 to 5 months and weighed between 1.3 to 2.3 kg. Animals were acclimated for 10 days prior to the start of treatment. Each animal was housed individually and cared for using standard caregiving protocols including regular environmental conditions, feeding schedules, and veterinary care. rAAV Vector Compositions and Formulations [0429] In this study, the panel of compositions comprising rAAV vectors containing an expression cassette encoding an eGFP transgene operatively linked to a CMV promoter are provided for intralacrimal injection under the conditions in Table 7. Each composition contains an rAAV vector with a different AAV capsid protein serotype. The compositions are labeled as OC-100a-d, each corresponding to a different AAV capsid protein serotype. Dose formulations for intralacrimal injection were prepared using clean procedures at the target concentrations described below in Table 9 by diluting with phosphate buffered saline solution. Table 7. Summary of rAAV Compositions 037525.00573 Intralacrimal Injection of rAAV Compositions [0430] Animals were dosed via intralacrimal injection on day 1 of the study. A summary of the formulation concentration for each composition tested, dose volume, dose frequency, and number of animals and lacrimal glands is found in Table 8. Prior to the injection, animals were anesthetized by intramuscular injection of dexmedetomidine (0.25 mg/kg) followed by an isoflurane/oxygen mix through a mask to maintain anesthesia, if necessary. A topical antibiotic was applied to each eye after dose administration. On day 9 of the study, animals were given intranasal administration of varenicline tartrate (50 µL per nostril of 1.2 mg/mL varenicline) to induce tear production. Table 8. Summary of Experimental Design Bioanalysis [0431] Blood was collected on Day 1 before dosing, and again on Day 8 and 9 (after the intranasal dosing at approximately 1 hour post dose) from an auricular vessel from all animals. Blood samples were placed on ice until plasma is separated by centrifugation. Plasma samples were separated into 250 µL aliquots and frozen at -80°C for subsequent analysis. 037525.00573 [0432] A Schirmer tear test were performed to collect eye moisture from the animals on Day 8 and 9. Test strips were placed inside the lower eyelid for approximately 1 minute. The paper was removed and placed into separate tubes and frozen at -80°C for subsequent analysis. [0433] Plasma samples and Schirmer’s test strips were analyzed for concentration of eGFP and eGFP mRNA concentration using a validated procedure at Syneos analytical laboratories. Immunohistochemistry of Lacrimal Gland Tissue [0434] Animals were euthanized on day 9 following collection of blood and eye moisture by intravenous injection of sodium pentobarbital. Five sagittal sections of the left eye and sections of the left and right lacrimal glands were prepared for immunohistochemistry (IHC) according to lab standard operating procedure. Lacrimal gland IHC samples were stained for eGFP and subject to microscopic evaluation. Results [0435] Microscopic evaluation was performed to determine the efficiency of eGFP expression in lacrimal gland tissues dosed in vivo with the rAAV compositions. Isolated positive acinar cells in the IHC samples had pink to red cytoplasmic staining indicative of GFP expression (FIGS. 8A-8K; exemplary staining indicated by black arrows). Positive eGFP expression was observed in for the rAAV composition containing an AAV2 capsid protein (OC-100a) at 6.2×10 12 GC/mL (FIG.8A), the rAAV composition containing an AAV5 capsid protein at both 1×10 12 GC/mL (FIG.8B) and 6.2×10 12 GC/mL (FIGS.8C-8H), and the rAAV composition containing an AAV9 capsid protein at 6.2×10 12 GC/mL (FIGS.8I-8K). Conclusion [0436] The results from this example show that rAAV vectors can be used to deliver an expression cassette to the lacrimal gland by direct injection. The results also show that rAAV vectors containing capsid proteins with at least the AAV2, AAV5, or AAV9 serotypes can be used to deliver an expression cassette to cells within the lacrimal gland. Furthermore, the results demonstrate delivery of an expression cassette containing a transgene operatively linked to a CAG promoter sequence results in expression of the transgene in the cells of the lacrimal gland. 037525.00573 Example 3: Expression of EGFP Transgene in Porcine Lacrimal Gland Delivered by rAAV via Intralacrimal Injection [0437] The study objective was to assess if the lacrimal gland is able to be leveraged as a method to modify or enrich the tear film with a protein of interest in pigs. Subsequently, in vivo study was performed to test if EGFP could be produced in the acinar cells of the lacrimal gland and then secreted into the tear film after delivery of an adenoviral vector consisting of a plasmid encoding eGFP. To get cDNA encoding EGFP into acinar cells, the approach was to inject the lacrimal gland with an adeno-associated virus (AAV) which contained cDNA encoding for secreted EGFP (secEGFP). To create each AAV of 2 different serotypes (2 and 9) for secEGFP, an AAV transfer plasmid was generated which contained between the inverted terminal repeats (ITRs) the essential elements for secEGFP expression. The DNA sequence between the ITRs was packaged into the AAV (FIG.7) that was manufactured. Design Analysis and Methodology [0438] Research grade AAVs for secreted EGFP (serotypes 2 and 9) were synthesized at Sirion and were provided at a stock concentration of 5x10 12 . The AAVs were in vitro tested by CJ Solutions using HEK 293T cells and ELISA to ensure that the manufactured AAVs would transduce cells. At Texas A&M, eight domestic pigs received a one-time intralacrimal gland injection of EGFP with the right (OD; oculus dexter) gland receiving a low dose and the left (OS; oculus sinister) gland receiving a high dose. Six weeks after the first injection, a second injection with AAV2 and AAV9 high doses were performed. The study assessed EGFP expression at Day 35. Following tear EGFP level confirmation, the study was terminated 8 weeks after the second injection to assess the presence of EGFP in the lacrimal glands and assess any potential inflammation or gland abnormalities. (Tables 9 & 10). In the study, nasal spray dosing was administered between weeks 3 to 4 (Table 11). Table 9: Study plan for in vivo study of AAV2-secEGFP and AAV9-secEGFP in domestic pigs. 037525.00573 Table 10: Injected dose and volume of AAV. 037525.00573 vg= viral genomes Table 11: OC-01 nasal spray dosing was from day 21 to day 28. mcg= micrograms [0439] Following the second AAV-secEGFP injection, tears were collected from each eye via Schirmer strips on day 82. Tears were collected by placing a Schirmer’s Tear Test strip in the lower conjunctival cul-de-sac and leaving in place for 2 minutes. Tear protein was extracted from the Schirmer’s Tear Test strip and mesoscale discovery (MSD) analysis was conducted to detect the presence of EGFP protein in the tears. [0440] Lacrimal gland was collected for ocular histopathology on Day 103 and samples were sent to Zyagen, Inc. (San Diego, CA) for EGFP immunohistochemistry (IHC). [0441] ELISA results showed that the AAV serotypes that were manufactured could transduce HEK 293T cells and produced secreted EGFP in vitro. EGFP expression in the tear samples was confirmed by MSD analysis 82 days after AAV transduction with eGFP some levels >400 pg/mL as well as by IHC (FIG.9). IHC indicated that EGFP expression was within the acinar cells with greater acinar cell infectivity observed for AAV2 compared to AAV9. Additionally, transduction of ductile epithelial cells was observed for AAV9 injected lacrimal glands (FIG. 10). Hematoxylin and eosin staining of pig lacrimal gland after repeat AAV injections did not show any inflammatory infiltrate, atrophy or edema (FIG.11). 037525.00573 [0442] Porcine lacrimal gland that is injected with either AAV2-secEGFP or AAV9- secEGFP expressed the EGFP transgene product in acinar cells as well as ductile epithelial cells. The EGFP that was expressed in the lacrimal gland was found to be secreted into the tear film. Additionally, no safety signals or inflammatory infiltrates were observed in any animals after repeat injections of AAV2 or AAV9 regardless if they initially received a low or high dose of AAV during the first injection. The results of this study demonstrate that the acinar cells of the lacrimal gland are a target for a gene therapy approach to modify and/or enrich the tear film. Example 4: Expression of rAAV Transgene in Porcine Lacrimal Gland in Combination with OC-1 Nasal Spray [0443] This example describes a study in pigs to assess expression of rAAV encoding a model protein following a single intralacrimal gland injection. The objective of the study is to determine expression of mRNA encoding the model protein (referred to in the Examples and Figures as “protein_A”) in the lacrimal gland and transgene protein levels in tears following a one-time injection of an AAV encoding protein_A (referred to in the Examples and Figures as “AAV-protein_A”) to transduce the porcine lacrimal gland. The study is further designed to confirm expression and secretion of protein_A following intralacrimal gland injection and to assess the relative amount of protein present on the ocular surface upon stimulating tear production with varenicline nasal spray. Varenicline (“OC-1”) is the following compound: [0444] The AAV-protein_A plasmid encodes from 5ʹ to 3ʹ an AAV2 5ʹITR, a CMV enhancer/promoter, an intronic sequence comprising a Kozak, an open reading frame encoding protein_A, a Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element, polyA sequence, and an AAV23ʹITR. [0445] The study parameters are detailed in Table 12. The administration and dosing are shown in Table 13. 037525.00573 Table 12: Study plan for in vivo evaluation of intralacrimal gland injection of rAAV in domestic pigs Table 13: Injected dose and volume of AAV AAV-protein A stock concentrations are 5 x 10 12 vg/mL and are provided in 500 µL aliquots and stored at -20 o C (short-term, <2 years) or -80 o C (long-term). In this study, there is only 1 dose, (1 x 10 11 vg). [0446] The timeline for the porcine study is shown in FIG.12. For all pigs (N=14), day 0 is the day of injection. Tears are collected from each eye via Schirmer strips (applied for approximately 2 minutes then removed) on days 7, 14, 21, 28, 35, 42, 60/61, and 90. Schirmer’s Strips are immediately cut above the fluid or dye line with a pair of scissors. The bottom portion 037525.00573 (tear saturated) of the Schirmer’s Strip is then placed in a microcentrifuge tube and kept on ice until transferred to freezer (-80℃). On days 14 and 42, tear collection occurs first and then nasal spray dose is administered. Approximately 2 minutes after administration of nasal spray dose a second day tear collection occurs. For days 22 to 28, OC-01 nasal spray is administered twice daily (at least 6 hours between administrations) to both nares on days 22 to 27 and once on day 28. Tear collection on day 28 will occur 2 minutes after administration of nasal spray. [0447] On day 90, gross pathology is performed and body weights are assessed. Additionally, one lacrimal gland from each animal is collected for ocular histopathology by immunohistochemistry (IHC). After harvesting the lacrimal glands, they are fixed in 10% formalin for 24 to 48 hours (at room temperature) then to 70% EtOH and store at 4℃. The volume in the tubes is maintained at 5 times that of the tissue and the tissue is fully submerged. [0448] A second lacrimal gland is collected, rinsed with phosphate-buffered saline and immediately placed in RNA-Later. The sample is snap frozen in liquid nitrogen. ~0.5-1cm square pieces of tissue from heart apex, kidney and liver are collected and immediately placed in a 2mL cryotube and snap frozen in liquid nitrogen. Cryotubes are later stored at -80℃ until shipped for mRNA analysis. [0449] mRNA analysis is performed to analyze AAV-derived gene expression of protein_A in the lacrimal glands of domestic pigs, using a developed one-step duplex RT-qPCR method. Each lacrimal gland is homogenized and lysates loaded into a QIASymphony for automated RNA extraction utilizing silica-based RNA purification, magnetic separation and enzymatic removal of DNA. The AAV-protein_A vectors contain the bovine growth hormone (bGH) polyA sequence at the 3’ untranslated region of the transgene. Protein_A mRNA is analyzed using primers and a probe targeting the bGH poly A sequence, with sequences shown in Table 14. Amplification is for 76 bp of the bGH sequence. The extracted total RNA samples are analyzed for both bGH mRNA copy numbers and the Ct values of porcine endogenous Hprt1 mRNA on 96-well plates using the QuantStudio 7 Flex Real Time PCR system and a one-step duplex RT-qPCR method (see Table 15). Each plate includes a standard curve, negative controls and quality control samples, which are prepared separately to avoid cross- contamination. Each standard curve includes bGH standard DNA levels at 108, 107, 105, 104, 103, 102, 50, 25 and 0 copies per well. RT-qPCR of the RNA samples is performed in duplicate wells up to 100 ng per well. The bGH mRNA copy number in each RT-qPCR well is interpolated from the bGH DNA standard curve (Acceptance Criteria: R2 ≥ 0.980). A two-fold multiplication step is used to adjust for interpolating single stranded (ss) mRNA from the 037525.00573 double stranded (ds) standard curve, and the mean copy number of the two replicate wells will be reported as copies of ss bGH mRNA per 100 ng of RNA sample. In addition, each RNA sample is tested using qScript XLT One-step RT-qPCR (without added reverse transcriptase) to monitor the potential vector DNA contamination in the RNA samples. Table 15: RT-qPCR assay conditions Reagent Final concentration 2x qScript XLT One-Step ToughMix Master Mix* 1x bGH-F3 Forward Primer 200 nM bGH-R3 Reverse Primer 800 nM bGH-P3 Probe 150 nM Porcine Hprt1-F1 Primer 200 nM Porcine Hprt1-R1 Primer 800 nM Porcine Hprt1-P1 Probe 150 nM Porcine lacrimal gland matrix RNA** 100 ng bGH Standard DNA** 0 – 10 8 copies Nuclease-free water To final volume of 20 µL *ToughMix is replaced with One-Step RT-qPCR Master Mix, without reverse transcriptase, when analyzing RNA samples for monitoring potential vector DNA contamination. * * * * [0450] In closing, it is to be understood that although aspects of the present specification are highlighted by referring to specific embodiments, one skilled in the art will readily appreciate that these disclosed embodiments are only illustrative of the principles of the subject matter disclosed herein. Therefore, it should be understood that the subject matter described herein is in no way limited to a particular compound, composition, article, apparatus, methodology, protocol, and/or reagent, etc., described herein, unless expressly stated as such. In addition, those of ordinary skill in the art will recognize that certain changes, modifications, permutations, alterations, additions, subtractions and sub-combinations thereof can be made in accordance with the teachings herein without departing from the spirit of the present specification. 037525.00573 [0451] Use of the terms “may” or “can” in reference to an embodiment or aspect of an embodiment also carries with it the alternative meaning of “may not” or “cannot.” As such, if the present specification discloses that an embodiment or an aspect of an embodiment may be or can be included as part of the inventive subject matter, then the negative limitation or exclusionary proviso is also explicitly meant, meaning that an embodiment or an aspect of an embodiment may not be or cannot be included as part of the inventive subject matter. In a similar manner, use of the term “optionally” in reference to an embodiment or aspect of an embodiment means that such embodiment or aspect of the embodiment may be included as part of the inventive subject matter or may not be included as part of the inventive subject matter. Whether such a negative limitation or exclusionary proviso applies will be based on whether the negative limitation or exclusionary proviso is recited in the claimed subject matter. [0452] Notwithstanding that the numerical ranges and values setting forth the broad scope of the invention are approximations, the numerical ranges and values set forth in the specific examples are reported as precisely as possible. Any numerical range or value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Recitation of numerical ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate numerical value falling within the range. Unless otherwise indicated herein, each individual value of a numerical range is incorporated into the present specification as if it were individually recited herein (e.g., any disclosure of a range with integer endpoints should be interpreted as also describing subranges defined by any pair of integers within the broader range). [0453] The terms “a,” “an,” “the” and similar references used in the context of describing the present invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Further, ordinal indicators—such as “first,” “second,” “third,” etc.—for identified elements are used to distinguish between the elements, and do not indicate or imply a required or limited number of such elements, and do not indicate a particular position or order of such elements unless otherwise specifically stated. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein is intended merely to better illuminate the present invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the present 037525.00573 specification should be construed as indicating any non-claimed element essential to the practice of the invention. [0454] When used in the claims, whether as filed or added per amendment, the open-ended transitional term “comprising” (and equivalent open-ended transitional phrases thereof like including, containing and having) encompasses all the expressly recited elements, limitations, steps and/or features alone or in combination with unrecited subject matter; the named elements, limitations and/or features are essential, but other unnamed elements, limitations and/or features may be added and still form a construct within the scope of the claim. Specific embodiments disclosed herein may be further limited in the claims using the closed-ended transitional phrases “consisting of” or “consisting essentially of” in lieu of or as an amended for “comprising.” When used in the claims, whether as filed or added per amendment, the closed-ended transitional phrase “consisting of” excludes any element, limitation, step, or feature not expressly recited in the claims. The closed-ended transitional phrase “consisting essentially of” limits the scope of a claim to the expressly recited elements, limitations, steps and/or features and any other elements, limitations, steps and/or features that do not materially affect the basic and novel characteristic(s) of the claimed subject matter. Thus, the meaning of the open-ended transitional phrase “comprising” is being defined as encompassing all the specifically recited elements, limitations, steps and/or features as well as any optional, additional unspecified ones. The meaning of the closed-ended transitional phrase “consisting of” is being defined as only including those elements, limitations, steps and/or features specifically recited in the claim whereas the meaning of the closed-ended transitional phrase “consisting essentially of” is being defined as only including those elements, limitations, steps and/or features specifically recited in the claim and those elements, limitations, steps and/or features that do not materially affect the basic and novel characteristic(s) of the claimed subject matter. Therefore, the open-ended transitional phrase “comprising” (and equivalent open- ended transitional phrases thereof) includes within its meaning, as a limiting case, claimed subject matter specified by the closed-ended transitional phrases “consisting of” or “consisting essentially of.” As such embodiments described herein or so claimed with the phrase “comprising” are expressly or inherently unambiguously described, enabled and supported herein for the phrases “consisting essentially of” and “consisting of.” [0455] All patents, patent publications, and other publications referenced and identified in the present specification are individually and expressly incorporated herein by reference in their entirety for the purpose of describing and disclosing, for example, the compositions and 037525.00573 methodologies described in such publications that might be used in connection with the present invention. These publications are provided solely for their disclosure prior to the filing date of the present application. Nothing in this regard should be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention or for any other reason. All statements as to the date or representation as to the contents of these documents is based on the information available to the applicants and does not constitute any admission as to the correctness of the dates or contents of these documents. [0456] Lastly, the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention, which is defined solely by the claims. Accordingly, the present invention is not limited to that precisely as shown and described.

037525.00573 SEQUENCE TABLE 037525.00573 037525.00573 037525.00573 037525.00573 037525.00573 037525.00573 037525.00573 037525.00573 037525.00573 037525.00573 037525.00573 037525.00573