Results obtained by our research group during the last grant period suggest that PGs may play an important role in lens pathophysiology and implicates lens PG biosynthesis with development of cataract. However, it is unclear how manipulation of lens PG levels could modulate lens function to maintain lens transparency. Aspirin-like drugs, which inhibit PG synthesis, delay human cataract development. Our published reports indicate that a decreased PG synthesis is also associated with the development of galactose induced cataractogenesis. This proposal will examine the discrepancy in relating PG synthesis to development of cataract and determine the physiological role of PGs in lens development. Different models of cataract production (eg. streptozotocin and x- irradiation) will be used to determine if altered lens PG biosynthesis is a common feature in cataract. The leukotrienes, like the PGs may also play a role in the physiology of the lens. The relevance of our findings is limited until we understand the role of eicosanoids in modulating lens physiological functions and concomitantly whether the human lens can generate PGs. This study will examine the role of eicosanoid production in development, aging and cataractogenesis using biochemical, pharmacological, microchemical and tissue culture techniques. The role oftens PGs in mitosis, cyclic nucleotide metabolism, and ion transport will be examined in both young and old rats, as will the effects of PG inhibitors in modifying lens cellular function and cataract onset. The ability to regulate lens eicoanoid synthesis might, in the long term, lead to a rational therapy for delaying the onset of human cataract.
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