Over the last 5-6 years there has been an increase in the incidence of cataracts in salmon farming.

Serious outbreaks of the disease have been observed in Norway, United Kingdom and Ireland.

Cataract may be defined as opacification of the lens and/or lens capsule. It is common to distinguish between Osmotic cataract and Irreversible cataract. The former appears as a poorly demarcated opacity around the anterior, vertical lens suture and these changes may disappear if osmotic balance is re-established, provided that the changes have not been too extended or long lasting. Irreversible cataract is a common cause of reduced vision or blindness in farmed fish as well as in other species. As salmon are dependent on vision for normal food intake, even moderate cataract changes will affect the growth rate of the fish.

It is not known what causes the cataracts that are observed in modern salmon farming. However, reports in the literature describe some known causes of cataracts and these have been related to nutritional, environmental and physical factors. Deficiencies of specific nutrients such as methionine, cysteine, tryptophane, riboflavine (Vitamin B2), vitamin A and zinc have previously been discussed as possible causes of cataracts. Such deficiencies were more common in the early days of fish farming, but may also occur during modem intensive farming conditions. In periods with rapid growth it is also possible that the lens is not able to absorb sufficient amounts of nutrients needed for normal lens growth, metabolism and protection. Another cause might be parasitic invasion, though mainly observed in farmed trout. It may also occur in other farmed species. Toxic factors, for instance specific anti-parasitic treatments have been described as causes of cataracts. Changes in water quality may also lead to cataract. Exposure to sunlight has been reported to cause cataract in trout. Thus the causes of cataracts in farmed fish are rather difficult to determine and may vary depending on several factors as indicated above. To recommend special treatment, change of operating conditions during farming or choice of special feeds has therefore been a problem.

Cataracts is a well known problem for several species and also for humans and in the literature several treatments to the disease have been discussed and recommended. Thus, it is generally known from Russian Patent No. 2,071,316 to treat human and animal cataracts with eye drops containing a beta-alanyl-L-histidine.

Fish feed contains protein comprising amino acids, including histidine. The amino acid profile may vary and the amino acid requirement for Atlantic salmon has not been established. Essential amino acids must, however, be present for normal growth according to Handbook of Nutrient Requirements of Finish, Robert P. Wilson, CRC Press, Boca Raton Ann Arbor Boston London.

According to"Nutrient Requirements of Fish, Commitee on Animal Nutrition, Board of Agriculture, National Research Council, National Academy Press, Washington D. C. 1993, the requirement of amino acids is considered to be about the same for Atlantic salmon as for Pacific salmon and is stated on page 63 to be 0.7 weight% histidine of the feed, for rainbow trout and 0.61 weight% histidine for Pacific salmon. In commercial diets histidine levels of 0.8-1.0 % have been observed. As amino acids are natural components of fish feed, there are also several patent publications mentioning the level of amino acids, including histidine, in their feed. However, none of these mention treatment of eye diseases by balancing the amino acid or histidine content of the feed. Of such publications the following are referred to: JP 61096959 describing food for rearing fish obtained by injecting liquid nutrients, e. g. vitamins, minerals, organic acids and amino acids comprising histidine, to raw or thawed fish and JP 51013696 relating to Fish breeding feed preparation. 0.5% lysine or its salt, 0.2% of histidine or its salt and 0.4-4% argine or its salt were added to the feed raw material. The resulting product can be used in the form of powder, granules and pellets. Growth of tunny, horse mackerel and sea bream is remarkable.

Handling of the feed is simple compared to live feed. Storage of the feed is easy.

The main object of the invention was to identify nutrient elements that could be used to reduce occurrence of cataracts in farmed fish and to develop a feed containing such elements.

In their search for a solution to the problem the inventors started by studying the history of fish farming and of occurrence of various diseases and their possible causes. Physical conditions, including stress conditions, may cause diseases or increase their occurrence. Changes in dietary compositions were also examined. The increasing incidence of cataracts in salmon farming in European countries has by some been related to the omission of blood meal in commercial diets, from 1995 in Norway. Some feed producers omitted blood meal from their feed already in 1990-1991 without observing any apparent problem. Blood contains significant amounts of iron, zinc and amino acids. Following the incidence of Creutzfelt-Jacob disease and possible relations to BSE in cattle, use of by-products from mammalian sources in breeding have been debated internationally. This has led to a general uncertainty in the fish farming industry and since blood meal may not be accepted as a feed ingredient in the future, it is essential to examine whether the omission of blood meal from the fish feed may have had negative effects. Experiments were therefore started to study the effects on the fish and in particular on the occurrence of cataracts as a function of type of feed. Tests to investigate the effect on cataracts of addition of blood meal to the feed were performed. The first experiment with adding blood meal to the feed gave no clear results on cataract occurrence, but then a series of tests were started to more thoroughly study the possible effect of the feed containing relatively high contents of blood meal. These experiments did not show any significant effect on growth, but the cataract incidents were significantly reduced. The obvious difference between blood meal and fish meal is the amino acid profile.

Among the most essential amino acids, the histamine content is substantially higher in blood meal (average 5.65%) than in fish meal (average 1.78) according to Degauss data base (ammonite 1.0) for"The amino acid composition of feed ingredients". Further experiments were therefore conducted focusing on the histidine content of the feed and the possible effect thereof on occurrence of cataracts. It was then found that normal histidine content in the feed (about 0.8%) did not have any effect on the cataract occurrence, but when about twice as much histidine was used in the feed the occurrence of cataracts was significantly reduced. Already at a histidine content of 1.17% the % eyes with cataracts were less than half of that for a histidine level of about 1 %. The effects of other amino acids seemed to be negligible.

In view of the recommendations for treatment of cataracts for humans being that the histidine should be administered by eye drops, it is quite surprising that the observed effect on cataracts of fish can be reduced from about 55% to 5% by just increasing the histidine content in the feed to about twice the normal level. None of the publications stating a certain amino acid and histidine content in the feed in order to obtain higher growth indicate anything about these components on cataracts. On the contrary, one of the possible causes suggested for cataracts is intensive farming conditions such as use of growth stimulants and according to the publications relating use of amino acids and histidine the claimed effect is increasing growth. Accordingly, addition of histidine to the feed as stated in these publications should lead away from increasing the histidine content in the fish feed in order to reduce the occurrence of cataracts. In spite of this, the experiments with addition of histidine to feed for salmonids were continued in order to possibly verify the positive indications of the initial experiments. It was then found that by increasing the histidine content of the total feed substantially the cataract occurence could be markedly reduced.

The upper limit for the histidine level seemed to be rather a practical one, but should be about 2 weight%. Histidine within the meaning of the invention encompasses each of D-histidine and L-histidine, racemic or non-racemic mixtures of histidine or salts thereof.

The effects on zinc and iron content in the feed seemed to be of minor importance as long as the level for these components were within normal levels for commercial feeds.

Figure 1 shows the % eyes with cataracts as function of diet and dietary histidine level.

Figure 2 shows cataract severity as % of the lens area covered by cataract as function of diet and dietary histidine level.

The main features of the invention are that the feed for salmonids should contain more than 1.15% histidine, or corresponding amounts of histidine pre-cursors or histidine derivatives such as anserin, carnosin or ergothionein, of the total weight of the feed in order to obtain a reduction of cataracts. The most preferred content of histidine in the feed will be 1.3-2.0% of the total feed.

It is also preferred that the feed contains more than 120 mg zinc/kg feed.

The invention is further explained and elucidated in the examples and the figures.

The scoring system employed for assessing degree of cataract in Examples 1 and 2 was as follows: 0 clear lens 1 minor part of the lens affected (<10%) 2 minor to medium part of the lens affected (10-50%) 3 major part of the lens affected (50-75%) 4 completely opaque lens Total cataract score for each fish was noted as the combined score for both eyes (i. e. 0-8). In some of the examples the accumulated score for each group of fish is shown (i. e. combined cataract score for each fish x number of fish affected).

In Example 3 the diameter of the cataract in each eye was measured to the nearest 0.1 mm while observing the eye, illuminated from the side with a fibre optic light source, using a binocular microscope. From this measurement, the area of the cataract was determined by calculation. At the same time, the length of each fish was measured from the nose to the fork of the tail. This body length measurement was used to calculate the total area of the upper hemisphere of the lens that would be visible if the lens had been removed from the eye. The area of the upper hemisphere of the lens had previously been determined with a separate sample of fish to be related to fish length by the relationship.: Area (mm2) =12.56* (1.32+0.032* (fish length in cm)) 2.

Using the area of the cataract, calculated from the measured cataract diameter, and the area of the excised lens, calculated from the body length of the fish sampled, the cataract severity was expressed as a % of the whole lens area that was affected. Between 35 and 50 fish were examined from each replicate tank on each dietary treatment, the incidence of eyes with cataract was noted, and the mean value for the size of the cataract in those affected was calculated to give the cataract score as cataract %.

Example 1 Atlantic salmon with initial mean weight of 40-50 grams were placed in fresh water tanks, 500 fish in each. Three different diets were used during the experiment. Control diet, positive control (PC) being a feed with added blood meal and new diet (ND) being a feed according to the invention. Feeding was in excess of requirement with automatic feeders. A total number of 180 fish were sampled from each dietary treatment. In Table 1 the chemical compositions of the diets are shown and in Table 2 the cataract scores per dietary treatment are shown.

Table 1 Diets Control PC ND Protein (%) 46. 2 46.6 47.3 Fat 19. 7 19.1 19.8 Minerals (mg/kg) 261Iron78 257 Zinc 136 160 450 Amino Acids (% of diet) Histidine 0. 9 1. 2 1.5 Methionine 1. 1 1.0 1.1 H-Cystine 0. 4 0.4 0.4 Proline 1. 6 1.6 1.5 Lycine 3. 1 3.1 3.1 Table 2 Diet No. Examined No. Affected Cataract score Control 180 94 192 PC 180 72 95 ND 180 74 104 From this experiment it was found that there was no significant effect of diet on number of affected fish, but a significant effect of diet on cataract score.

Example 2 This example shows the results from a series of experiments performed with different diets over a period of four months. Atlantic salmon with an average initial weight of 90 grams were used. 12 cages (12x12 meters) were applied, each containing 3000 fish. The fish were hand fed in excess of calculated requirements. The chemical composition of the diets are shown in Table 3 and the cataract frequency at each screening (% of fish with cataracts) is shown in Figure 1.

The diets used were: PC, positive control containing blood meal; NC, negative control; ND, a diet according to the invention; OB, a commercial feed. In Table 3 two sets of diets used in each group for the duration of the experiment are shown (PC1, ND1, NC1 and OBI during the first part of the experiment and PC2, ND2, NC2 and B02 during the second part). In Table 4 the cumulative cataract score (number of fish affected x cataract score) is shown.

Table 3 Diet PC1 ND1 | NC1 | OB1 | PC2 ND2 NC2 OBI Protein (%) 45. 9 45.1 46.6 45.5 38. 1 41. 0 42. 1 41.9 Fat (%) 25.6 25.7 26.0 27.1 35.2 30.7 30.7 30.1 GE (MJ/kg) 20.9 20.9 21.3 21.3 22.9 21.8 22.1 21.8 Minerals(mg/kg) Iron 255 144 156 391 228 109 133 Zinc 147 268 204 222 124 173 149 178 Amino Acids (% of diet). Histidine 1.0 1. 3 0.8 0.8 Methionine 0.9 1.0 1.5 1.0 1.1 1.0 1.2 0.9 H-Cystine 0.4 0.4 0.7 0.5 0.4 0.4 0.4 0.5 Proline 1.9 1.8 1.8 2.3 1.7 1.7 1.7 2.2 Lycine 2.9 2.9 3.0 2.4 2.3 2.5 2.6 2.1 Table 4 Diet June July August September PC 20 35 37 51 ND 17 30 47 60 OB 21 44 59 70 NC 23 47 70 83 In June 60 fish were sampled from the PC and ND groups, 90 from OB and NC.

In July 60 fish were sampled from the PC group, 90 from the other groups.

In August 90 fish were sampled from each dietary treatment.

In September 180 fish were sampled from ND, OB and NC, 120 from PC.

From this example it is clear that the cataract occurrence is rather complicated and varies not just by the feed used but also with the age of the fish and other conditions during the farming period.

However, the experiments clearly show that when the histidine content of the feed is relatively high, the cataract occurrence is at its lowest.

Example 3 Five diets were used during this experiment. Diet 1 had high inclusions of bovine blood meal and corresponding high histidine level. Diet 2 was a commercial diet with added blood meal. Diet 3 was one of the diets within the invention. The amino acid concentrations, in % of the dietary protein, for the various diets are shown in Table 5. The results of the experiments, based on dietary histidine content (%), are shown in Figures 1 and 2.

Table 5 AminoAcids Diet 1 Diet 2 Diet 3 Diet 4 C steine 0. 97 1. 05 1. 04 1 05 Methionine 2. 14 2. 03 2. 47 3.06 Aspartic Acid 8. 27 8. 92 8. 91 8. Threonine 3. 58 3. 64 3. 79 3.83 Serine 4. 09 4. 45 4. 30 4.52 Glutamic Acid 13. 14 14. 92 13. 96 14.24 Proline 4. 76 4. 69 4. 41 0 4. 5.195.695.67Glycine6.09 Alanine 6. 38 5. 74 5. 89 5.89 Valine 5. 41 5. 67 5. 05 4.91 Isoleucine 3. 63 3. 68 4. 34 4.24 Leucine 8. 16 7. 96 7. 47 7.41 Phenyalanine 4. 35 4. 67 4. 25 4.17 3.002.582.26Histidine3.36 Lycine 6. 60 6. 91 7. 01 7.07 Arginine 5. 32 5. 54 5. 80 5.83 % histidine in diet 1. 68 1. 31 1. 17 1.04 % protein in diet 49. 9 43.71 45.36 46.00 From Figures 1 and 2 it can be seen that there is a substantial difference between feed containing about 1% and 1.17% histidine with regard to occurrence of cataracts. When the histidine content of the feed is increased to 1.68, the occurrence of cataracts is reduced to about 5% contrary to about 56% when the feed contains only 1.04 % histidine.

Thus the inventors have been able to arrive at a new feed which can be used to reduce cataracts in salmonids under conditions which would result in substantial occurrence of cataracts if the fish was fed with conventional feed. The new feed does not reduce the growth of the fish compared to conventional feed.