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 polypeptides of the retinal pigment epithelium (RPE) capable of evoking experimental uveitis. A membrane fraction was prepared from purified bovine RPE cells. The Triton X-100 soluble protein fraction was separated into polypeptide fractions by preparative gel electrophoresis, and the pathogenicity of the main isolated polypeptides was investigated in Lewis rats. After immunization, two hitherto unknown pigment epithelial polypeptides with M(r) 28/30 kD (doublet) and 43 kD (PEP-28/30 and PEP-43, respectively) elicited progressive pigment epitheliitis and choroiditis accompanied by extending plaque-shaped macrophage accumulations along the RPE-Bruch's membrane layer. No inflammatory foci were found within 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) appeared to be non-uveitogenic at the tested dose. PEP-28/30 and PEP-43 exhibited a partial antigenic relationship to PEP-65. PEP-28/30 exhibited marked reactivity to a monoclonal antibody previously raised to a 32 kD RPE-specific protein.

in addition to the previously described main RPE-specific membrane polypeptide PEP-65, the RPE appears to contain two more uveitogenic components, the intrinsic pigment epithelial membrane polypeptides PEP-28/30 and PEP-43. Like PEP-65, these antigens are able to evoke experimental autoimmune pigment epithelial protein-induced uveitis (EAPU) in rats.