Studies in this proposal are important because cataracts are the 3rd leading cause of blindness in man in the United States. However, the biochemical mechanism for most cataracts is unknown. Studies in this proposal are designed to elucidate underlying biochemical mechanisms for cataract formation. This will be accomplished by use of an extremely convenient animal model of cataract, the selenite overdose cataract. The long-term objective of this proposal is to provide a biochemical mechanism for selenium-induced cataract. Severe nuclear cataracts are produced in only 4 days by a single injection of an overdose of the essential trace mineral selenium (as sodium selenite) into young rats. The specific hypothesis to be tested is that selenite cataracts are caused by initial attack of selenite on lens epithelium, leading to calcium influx, activation of proteolysis, and insolubilization of lens proteins. Experimental set I (Proteolysis) will study the origin of insoluble polypeptides in selenite cataract, involvement of proteolytic enzymes and lens protein insolubilization processes. Experimental set II (Calcium) will study association of free calcium with localized opacities, permeability of lens to calcium, integrity of calcium and sodium pumps. Experimental set III (Epithelium) will study effect of selenite on cultured epithelium, and the role of the epithelium in development of the newly characterized selenite cortical cataract. These studies will provide a clear-cut biochemical mechanism for selenite cataractogenesis. Hopefully, such knowledge would indicate avenues leading to prevention and treatment of cataract in man.
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