PEROXIDES AND ARACHIDONATE METABOLISM IN ANTERIOR UVEA

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DESCRIPTION: Although hydrogen peroxide (H2O2) is present in several tissues of the anterior segment of the eye, its pharmacological/toxicological functions is yet to be fully determined. Evidence from the PI's laboratory reveals that H2O2 can potentiate sympathetic neurotransmission in the iris-ciliary body of several mammalian species, an effect which is dependent on the age of the animal. The present project will test the hypothesis that both cyclooxygenase (COX) and non-COX products of arachidonic acid metabolism mediate some of the pharmacological/toxicological effects of H2O2 in the anterior uvea. The overall objective of the present study is to determine the role of prostanoids and isoprostanes (IsoP's) in the pharmacological/toxicological effects caused by H2O2 in the anterior uveal tissues both in vitro and in vivo. Experiments have been designed to answer the following questions? (a) are prostanoids and IsoP's involved in the pharmacological/toxicological effects of H2O2 on sympathetic neurotransmission and on postjunctional responses of anterior uveal tissues to pharmacological agents in vitro? (b) does exogenously applied H2O2 increase the production of prostanoids and IsoP's in the iris-ciliary body followed by washout of these compounds into the aqueous humor? (c) can endogenous concentrations of H2O2 in the anterior uveal tissues be increased up to a level where it can stimulate the production of prostanoids and IsoP's? (d) does in vivo biochemical changes induced by exogenous and endogenous H2O2 correlate with morphological alterations of anterior uveal tissues by this oxidant? The result of this study will improve our understanding of the basic mechanisms involved in the effects of H2O2 on anterior uveal tissues and may reveal a new role for this oxidant in the pathophysiology/toxicology of the eye. The PI anticipates that the findings of this project will be applicable to diseases of the anterior segment of the eye such as glaucoma, uveitis or cataract.