The present study is to investigate further the role of oxidative stress via oxygen activation in cataract formation and to devise appropriate biochemical means of preventing such cataract developing using nutritional and metabolic antioxidants. The studies will be conducted in vitro as well as in vivo using primarily rats, normal and acatalasemic mice, and guinea pigs. Since hydrogen peroxide is one of the centrally active oxidants, its level will be determined in lens, aqueous and vitreous as a function of aging and in conditions known to promote cataractogenesis, such as hyperoxia, diabetes, galactosemia and sodium selenite administration. The mechanism of peroxide generation will also be studied by in vitro culture experiments. The absence of cataracts in the acatalasemic mice provides a good opportunity to investigate further the enzymatic and nonenzymatic defenses involved in cataract prevention. Hence, the lenses from the mice maintained under normal or hyperbaric oxygen (HBO) will be studied for their peroxide content as well as for the contents of various enzymatic and nonenzymatic constituents. These findings should provide further valuable information on the pathophysiology of cataracts. It has been observed that some cataracts are preventable by the exogenous use of antioxidants like vitamin E, vitamin C, pyruvate and bioflavonoids. Since these agents are nontoxic, additional studies are likely to be useful towards the development of medical therapy against this disease. Since the role of vitamin C as an anticataractogenic substance is disputable at present, further studies will be undertaken in normal and scorbutic guinea pigs, before and after exposure to HBO. The extent of physiological damage as reflected by the lens levels of GSH, ATP, malonaldehyde and protein carbonyl contents as markers of oxidative stress will be determine. The pathophysiological effects will be ascertained in vitro by measurements of Rb+ uptake by the lens, and in vivo by retinoscopic functional assessment. Studies on the antioxidant and anticataractogenic effects of pyruvate will be extended to other ketoacids. Due to slower metabolism, their antioxidant effects are likely to be more prolonged. In addition, they inhibit aldose reductase and consequently decrease polyol accumulation. This dual mode of action is similar to that of the flavonoids. Hence, these compounds will be studied further for their effect against oxidative stress as well as against sugar cataract formation in vitro and in vivo.
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