The long-term objective of this project is to study proteins in the retina and uveal tissues which are involved in the onset and regulation of ocular inflammatory diseases such as experimental autoimmune uveoretinitis (EAU). In this application, EAU induced by retinal S-antigen (S-Ag) in rats and related events are studied with a particular focus on immunosuppression. There are four specific aims. 1. We have recently found that inoculation of the testis (immunologically privileged organ with tolerance to alloantigen) with S-Ag suppresses the onset of EAU induced by subsequent S-Ag immunization m footpads. The orchidic treatment appears to activate systemic immune responses such as inhibition of delayed type hypersensitivity. The mechanism of the systemic immunosuppression will be investigated. 2. We have separated novel proteins from porcine ciliary epithelium, iris, and vitreous body that inhibit lectin-stimulated lymphoproliferation. Similar proteins are found in a variety of tissues and may represent a new class of lymphokines or immunodulators. Preliminary studies indicate that these proteins inhibit expression of interleukin II receptors on mitogen-stimulated lymphocytes. Ocular proteins will be purified and characterized. 3. Transforming growth factor beta (TGF-beta) appears to accumulate in the basement membrane (BM) of ciliary vascular endothelium in EAU. A hypothesis that TGF-beta regulates the formation of BM substances and their attachment to the cells and modulates the inflammatory process of anterior uvea will be examined by immunohistological methods using antibodies against TGF-beta, fibronectin, collagens, etc. 4. An S-Ag-like protein extractable from porcine ciliary epithelium and vitreous will be purified and its cellular location determined by immunocytochemical methods. The protein appears to be present in the nuclei of ciliary epithelial cells, basement membrane associated with the epithelial cells and vitreous and reacts specifically with anti-S-Ag MAb recognizing residues 308-316 of bovine S-Ag.
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