The long term objectives are to elucidate the mechanisms of transport of various substances into and out of the lens and across the blood-aqueous and blood-vitreous barriers and to assess how the abberations in these mechanisms contribute to the pathogenesis of cataract and other ocular abnormalities. The multifaceted approach to this broad program involves studies of the metabolism and function of glutathione in lens and other ocular structures in relation to membrane permeability, active transport, oxidative damage, and lens protein aggregation. The origin of H202 in aqueous humor of various species, its role in cataract formation and the mechanism of its detoxification by the lens will be examined. The role of glycoproteins and other membrane components in lens permeability will be investigated in genetic cataracts in Philly mouse and in cataracts induced by X-ray, tryptophan- and selenium-deficiencies as well as in human lens. Other aspects of these studies are concerned with the effect of cations on protein synthesis in X-ray cataract, and the multiple effect of low levels of X-ray and other cataractogenic insults in experimental animals. Investigations of transport characteristics of amino acids across blood-aqueous and blood-vitreous barrier will be continued and extended; these approaches utilize in vivo transport into ocular chambers in rabbits as well as isolated ciliary body in vitro and arterially perfused enucleated eyes. The study to establish a number of biochemical parameters, such as free amino acids, glutathione, cations and the enzymes of glutathione metabolism and hexosemonophosphate shunt in human lens will be continued. In addition to providing new knowledge on the biochemistry of the human lens correlation between the changes in these parameters and the nature and degree of opacity in human senile cataracts, classified according to Cooperative Cataract Research Group criteria, will be sought through the use of the Prophet computer system. While the proposed studies on the lens bear directly on the etiology of experimental and human senile cataracts, those concerned with blood-aqueous barrier are relevant to intraocular fluid dynamics and thus to glaucoma.
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