The objective of the proposal is to study in greater detail the significance of intraocular generation of active species of oxygen and consequent oxidative stress in the pathogenesis of cataracts. In vitro studies will be conducted with rat lenses to determine the effect of various active species of oxygen on the physiology of the tissue in terms of ion and amino acid transport, as well as in terms of lipid peroxidation using the criteria of alkane liberation coupled with lipofuscin and malonaldehyde production. Emphasis will be laid on determining the role of OH in tissue damage through the use of appropriate radical scavengers. The ion transport measurements will be supplemented with the measurement of Na-K- ATPase activity of the tissue and LDH leakage by the tissue under oxidative stress. The studies will be conducted under photochemical as well as nonphotochemical systems. Since polyols are potent OH scavengers, studies will be conducted with lenses that are polyol deficient or enriched with polyols by incubating them with appropriate aldoses. Purified human and calf lens membranes will also be used to determined their susceptibility to active oxygen species. Prior to susceptibility studies, they will be examined for their basic fatty acid, phospholipids and lipofuscin components. Endogenous O2- and H2O2 production by the lens will also be measured by the tissue under oxidative stress. Possible induction of SOD and catalase will be studied under in vitro organ culture conditions as well in the intact animals exposed to hyperbaric oxygen. Further studies will be conducted to determine the function of lens and aqueous ascorbate in the maintenance of the HMP shunt. The role of ascorbate will also be evaluated in terms of its ability (DHA) to compete for NADPH involved in polyol synthesis and accumulation. Such a competition may perhaps have and effect on the rate of cataractogenesis induced by high sugar levels. In vivo studies will thus be conducted on the effect of ascorbate and other antioxidants against the development of sugar cataracts. Similar in vivo studies will be conducted on the effect of nutritional antioxidants on the progress of cataracts (senile) in emory mice. The monkey's aqueous humor will be analyzed for ascorbate and amino acid contents as a function of age.
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