The overall objective of this project is to explore the mechanisms of ocular inflammation with a view to the development of better therapeutic approaches to the management of the inflamed eye. The goals of the present study are to 1) identify and characterize receptors in the eye that are specific for arachidonate derived mediators of ocular inflammation, 2) evaluate the impact of the inflammatory process upon receptor characteristics, and 3) study the pharmacological and physiological impact of specific receptor antagonists and more traditional anti-inflammatory agents. Receptor localization will be accomplished by autoradiographic studies, and characterization of the receptor will be described by radioligand binding assays in vitro. In selected situations, receptor functionality will be evaluated by measuring cellular generation of second messengers, particularly cAMP. Both fresh tissue and tissue culture preparations will be used. We will explore modulation of eicosanoid production and receptors subsequent to inflammation induced by intravitreal injection of endotoxin and also by intracameral hydrogen peroxide injection. The inflammatory response will be evaluated by clinical appearance and a number of physiological responses such as increased vascular permeability and inflammatory cell infiltration. Vascular permeability is determined by protein leakage into the aqueous humor and also by anterior segment fluorescein angiography. Cellular infiltration is judged by direct cell counts in aqueous humor, tissue, myeloperoxide assay and histology. Modification of the inflammatory other response by specific receptor antagonists alone and in combination with other anti-inflammatory agents will be evaluated using clinical and pathophysiology parameters.
