Localization of specific autoantibodies in the retinal photoreceptor cell layer in experimental retinal autoimmunity

The presence and localization of autoantibodies was determined in strain 13 guinea pigs with experimental retinal autoimmunity (ERA) induced by immunization with rhodopsin and rod outer segments (ROS). Sera were obtained from rhodopsin-immunized and from ROS-immunized guinea pigs before, during, and after onset of clinical uveitis. Autoantibodies were detected by indirect immunofluorescent staining of autogenic retinas as well as normal guinea pig retinas. Sera from animals with clinical disease showed specific labeling of the photoreceptor cell layer of the retina. The rhodopsin autoantibody showed a more defined specificity than the ROS autoantibody staining, only the retinal photoreceptors and retinal pigment epithelium. Specific fluorescence was localized only in the retina, and not in any other ocular or nonocular tissues. Neither the rhodopsin nor the ROS antibodies stained the uvea. Sera from animals taken before the onset of clinical disease did not demonstrate the presence of retinal-binding autoantibodies. These findings suggest that photoreceptor-binding autoantibodies appear in the sera of animals immunized with rhodopsin and with ROS, but only in animals with clinical disease. However, these antibodies probably are not the primary cause of pathology, since previous passive transfer experiments (data not shown here) could not be achieved with anti-ROS or with anti-rhodopsin antibodies. These autoantibodies could occur secondarily as a response to the bovine antigens which cross-reacted with the autologous guinea pig antigens. Subsequently these antibodies could be of primary importance in further tissue alteration and destruction.