The objective of the proposal is to investigate the role of oxidative stress in the pathogenesis of cataracts. Emphasis will be places on aspects of oxidative stress concomitant to the intraocular generation of active oxygen species, particularly superoxide hydrogen peroxide and hydroxyl radical. The implications of light in the pathogenesis of cataracts through photocatalytic generation of the species will be examined. The stress will be evaluated in terms of the tissue's ability to perform active transport of cations, amino acids, and myoiniositol in vitro. Additionally, the contents of malonaldehyde, lipofuscin, conjugated dienes and fatty acids, as might be affected under conditions of oxidative stress, will be measured. Susceptibility of the tissue to stress will also be examined at the level of plasma and mitochondrial membranes in terms of malonaldehyde formation and oxygen consumption. In vivo studies will be conducted to determine if cataracts in the Emory mouse are due to oxidative stress and, if so, can the cataract be prevented by the use of vitamins E, C, and cysteine, the dietary antioxidants. The possible contribution of vitamin C nutrition in the maintenance of lens transparency will be examined through the measurement of the soluble and insoluble proteins, malonaldehyde, lipofuscin, and conjugated dienes in the lenses of guinea pigs, with or without diabetes, maintained on subliminal amounts of vitamin C. Diabetes is expected to act synergistically in the lens changes. The synergistic effect of light on oxidative damage in vivo will be studied by exposing guinea pigs maintained on a suboptimal dose of vitamin C, to excessive light.
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