PROSTACYCLIN AND THROMBOXANE-A2 IN OCULAR TISSUES

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We intend to determine the biosynthesis of prostaglandins (PGs) and the newly discovered compounds thromboxanes and prostacyclin (PGI2) in different ocular tissues like iris, conjunctiva, retina and lens from different species. Arachidonic acid is metabolized into three major compounds: (1) PGs of E and F type, which are now known to be involved in the mediation of inflammation; (2) PGI2, which is a potent vasodilator, stimulator of cAMP and an inhibitor of platelet aggregation; and (3) thromboxane-A2 (TxA2) which is a potent vasoconstrictor and thrombus forming agent. The interaction between these three arachidonic acid metabolites in normal and pathological conditions is not yet known. In this proposal we are particularly interested in whether the ocular tissues have an ability to synthesize these compounds in normal and pathological (inflammation) conditions. Also, we intend to study the influence of the age and species difference on this arachidonic acid metabolism. In addition, we want to extend our study in developing specific inhibitors of the enzymes which biosynthesize PGE2 and PGF2alpha, TxA2 and PGI2 from arachidonic acid. These studies will enable us to understand the changes in the biosynthesis of PGs, thromboxane and PGI2 in the normal and pathological ocular tissues, and therefore further understand the possible functional role of these compounds. The fact that these very biologically active endogenous substances have already been shown to be biosynthesized by certain ocular tissues indicates a possible role for these agents in ocular function.