Investigations are being conducted on the biochemistry of the sensory retina, pigmented epithelium, choroid, vitreous and lens in normal and disease states, particularly in animal models of human retinal degenerations and in human retinal diseases. Effects of nutrition, genetic background, and environmental lighting (or darkness) on incidence and progress of retinal degeneration and associated posterior subcapsular cataracts (PSC) are being studied in pink-eyed and black-eyed strains of Royal College of Surgeons rats. An objective is to discover the mechanisms of ocular disease in RCS rats and explore possibilities for prevention or therapy. By 9 mo. of age, a fourth of pink-eyed but not black-eyed rats have mature cataracts. Factors involved in initiation and maturation of the cataracts are being examined. Dark-rearing of pink-eyed rats has shown that light initiates the PSC, and increased light exposure at early ages has demonstrated light to be a powerful factor in maturation of the cataract. Light also increases the rate of retinal degeneration. An hypothesis of the mechanism of damage to retina and lens is that a product of rhodopsin bleaching (perhaps free retinaldehyde) may act as a sensitizer to generate singlet oxygen (1-0-2), which can oxidize vitamin E and polyunsaturated fatty acids (PUFA) of phospholipids of degenerating rod photoreceptors. PUFA are broken down to water soluble toxic aldehydes, which can further damage the retina and also traverse the vitreous and affect the lens. Such aldehydes are detected in RCS vitreous shortly before the PSC appear. Diets that prevent maturation of the cataracts in pink-eyed rats reared in subdued lighting (1-3 footcandles inside the cage) are: (1) a purified diet of the American Institute of Nutrition (AIN-76); (2) a commercial rodent diet plus 25% sunflower kernels; and (3) a vegetarian rodent diet. Significant prevention of initial PSC has been achieving with (a) AIN-76 diet fortified with antioxidant factors; and (b) dark rearing.
