Uveitis is one of the major causes of legal blindness in the United States. Animal models of uveitis indicate that tissue damage is caused by various chemical mediators, including reactive oxygen metabolites that are derived from the inflammatory cells that characterize this disease. Our preliminary studies revealed a unique phenomenon: In the presence of a soluble peptide(s) produced by retinal pigment epithelium (RPE), neutrophil generation of superoxide was suppressed. Also. histologic examination of human eyes enucleated for severe uveitis reveals preservation of choriocapillaris and the retina at the site of intact RPE, which is consistent with RPE protection of the choriocapillaris. Based on our preliminary data and the morphologic observations, we hypothesize that RPE cells generate a peptide (or peptides) that protects the retina and choriocapillaris in uveitis by down-regulating superoxide production. This hypothesis will be studied using cell cultures of RPE and a clinically relevant model of uveitis. We will test our hypothesis with the following Specific Aims: 1. Purify and characterize the RPE protective peptide (RPP). 2. Determine the presence of RPP in normal RPE. 3. Detect the presence of RPP during the acute and chronic phases of S- antigen induced uveitis (EAU). The results of this study would elucidate the role of RPE in the modulation of uveitis, and could potentially provide a new therapeutic approach to the management of this blinding disease.
