Oxidant and Anti-Oxidant Effects on Arachidonate Metabolism by Rabbit Ocular Tissues

ABSTRACT

Ocular tissues have the capacity to metabolize arachidonate to prostaglandins and related materials, such as hydroxy arachidonate derivatives (HETEs) which are potent mediators of the inflammatory response. Reactive oxygen species are also present during the inflammatory response, resulting in an altered oxidative environment within the eye. This study was designed to evaluate the possible impact of the oxidant hydrogen peroxide and anti-oxidants, ascorbic acid and glutathione, upon arachidonate metabolism. It was found that hydrogen peroxide was observed to potently inhibit arachidonate metabolism in the cornea, but not in the iris-ciliary body. This might be related to a more efficient detoxification of hydrogen peroxide by iris-ciliary body. Ascorbate appeared to have a general stimulatory influence upon arachidonate metabolism in the iris-ciliary body. In the cornea, ascorbate selectively reduced metabolism to HETE while enhancing the products generated by the cyclo-oxygenase pathway. In both cornea and iris-ciliary body reduced glutathione suppressed conversion of arachidonate to its active metabolites. These observations indicate that arachidonate metabolism in ocular tissues is sensitive to the oxidative environment.