The precise mechanisms involved in the immunopathological phenomena associated with uveitis are not yet clearly understood. Our hypothesis is that a small number of immunocompetent cells specific for antigen is responsible for amplification of the chronic ocular inflammatory response, which is composed of a vast majority of non-antigen-specific cells including macrophages, lymphocytes, and plasma cells. The major area of interrest in the proposed investigations will be concerned with two aspects which underlie this hypothesis: 1) the role of immunologically committed memory cells; and 2) the effect of their soluble product (lymphokines) in amplification of the inflammatory response. In our rabbit model system, we will investigate the intraocular production of a variety of lymphokines including interleukin 1, interleukin 2, macrophage Ia recruiting factor (MIRF), and interferon in both primary and recurrent uveitis. In other experiments we will passively immunize the eye, using syngeneic donor immune lymphocytes or syngeneic lymphoid tissue. Intravenous challenge with specific antigen in these otherwise naive recipients should result in uveitis. The time-sequence for these experiments will allow us to mimic the striking immunologic memory associated with human recurrent ocular inflammatory disease. Suppression of immunocompetent cell mitosis and immunocompetent cell ability to produce lymphokine mediators will be investigated using local infusion of pharmacological reagents (principally theophylline), to effectively block the amplifying effects emanating from the resident intraocular immunocompetent cells. An experimental model system for production of neovascular glaucoma will be investigated using a number of demonstrably angiogenic substances. These will include lymphokines of syngeneic origion, tumor angiogenic factor (TAF), or mediators of the immune response to non-diffusable antigen. These materials including the antigen would be concentrated in polymers implanted adjacent to the trabecular meshwork. Visual assay of iris and limbal neovascularization as well as sequential measurements of intraocular pressure will be used to monitor these experiments.
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