Eicosanoids are ubiquitous biological substances which have many potent actions throughout the body. In the eye, two classes of eicosanoids, prostaglandins and leukotrienes, are thought to be mediators of inflammation and may contribute to the regulation of intraocular pressure. When administered topically, they disrupt the blood-aqueous barrier and also influence intraocular pressure. In the proposed studies we will evaluate eicosanoid formation, metabolism and action in tissues of the inflow and outflow pathways of the eye and its modulation by pharmacologic agents used in the treatment of glaucoma. We will also examine the effects of laser irradiation of the iris and trabecular meshwork, other treatment modalities in glaucoma, on the release of eicosanoids into aqueous humor and its pharmacologic modification. Trabecular tissue, cells derived from this tissue and ciliary body tissue will be incubated in the presence and absence of radiolabeled arachidonic acid; the products formed will be measured either by radioimmunoassay or by conversion of radiolabeled substrate after separation of products by high performance liquid chromatography. The results of these studies will enhance our understanding of glaucoma (particularly primary open angle, inflammatory and steroid glaucoma) and its treatment with pharmacologic agents and the laser. They also will be relevant to our understanding of uveitis and its treatment with anti-inflammatory drugs, and cataracts and their prevention.
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