UVEITOGENIC 28 30 KD AND 43 KD POLYPEPTIDES IN PIGMENT EPITHELIAL MEMBRANES OF THE RETINA/

The purpose of this study was the search for new intrinsic polypeptide s of the retinal pigment epithelium (RPE) capable of evoking experimen tal uveitis. A membrane fraction was prepared from purified bovine RPE cells. The Triton X-100 soluble protein fraction was separated into p olypeptide fractions by preparative gel electrophoresis, and the patho genicity of the main isolated polypeptides was investigated in Lewis r ats. After immunization, two hitherto unknown pigment epithelial polyp eptides with M-r, 28/30 kD (doublet) and 43 kD (PEP-28/30 and PEP-43, respectively) elicited progressive pigment epitheliitis and choroiditi s accompanied by extending plaque-shaped macrophage accumulations alon g the RPE-Bruch's membrane layer. No inflammatory foci were found with in the neural retina. Polypeptide fractions with M-r 14-17, 25 and 32/ 34 kD (doublet) (PEP-14/17, PEP-25 and PEP-32/34, respectively) appear ed to be non-uveitogenic at the tested dose. PEP-28/30 and PEP-43 exhi bited a partial antigenic relationship to PEP-65. PEP-28/30 exhibited marked reactivity to a monoclonal antibody previously raised to a 32 k D RPE-specific protein. In conclusion: in addition to the previously d escribed main RPE-specific membrane polypeptide PEP-65, the RPE appear s to contain two more uveitogenic components, the intrinsic pigment ep ithelial membrane polypeptides PEP-28/30 and PEP-43. Like PEP-65, thes e antigens are able to evoke experimental autoimmune pigment epithelia l protein-induced uveitis (EAPU) in rats.