Experimental allergic uveitis: induction by retinal rod outer segments and pigment epithelium

EAU was produced in strain 13 guinea pigs after immunization with purified guinea pig retinal rod outer segments and with retinal pigment epithelium in mycobacterial adjuvant emulsion. The lesions of EAU appear as inflammatory infiltrates of the iris and ciliary body followed by choroidal inflammation, often with retinal photoreceptor degeneration. Specific antibodies are detected in the serum of a majority of the animals with clinical disease. Immunohistochemical staining of normal and inflamed eyes with serum from the immunized animals with uveitis demonstrates specific antigens localized in the outer segments. All immunized animals demonstrate delayed-type hypersensitivity characterized by skin reactions of mononuclear cells, by the in vitro inhibition of migration of peritoneal macrophages from the sensitized animals in the presence of specific antigen, and by antigen-specific lymphocyte stimulation. More pronounced delayed-type hypersensitivity reactions occurred during uveitis and indicated that cellular immunity correlates with clinical EAU, whereas no correlation was found with serum antibody. Successful experiments at transferring clinical disease passively with sensitized lymphocytes from animals with uveitis to normal recipients were conducted via the intravenous as well as intravitreal routes. No inflammatory reactions occurred after similar transfer of nonsensitized lymphocytes. The recipients of the passively transferred cells demonstrated both humoral and delayed type hypersensitivity to the retinal antigens. These findings suggest that the retinal rod outer segments and pigment epithelium are the sourve of significant antigens in autoimmune uveitis and retinitis.