Autoimmunity has been suggested as the mechanism of several eye diseases. This concept has been extensively investigated in connection with diseases of the uveal tract, particularly by sympathetic ophthalmia, but neither the nature of the offending antigen(s) nor the immunologic mechanisms have been defined. A similar situation obtains with the Vogt-Koyanagi-Harada syndrome, a disease with ocular changes histologically resembling sympathetic ophthalmia. The traditional view that sympathetic ophthalmia represents an autoimmune response to uveal pigment has also been considered a mechanism of VKH syndrome. Despite pigmentary disturbances in these conditions, however, there is little evidence to support the role of pigment as autoantigen. Objectives of the proposed research are to define the role of specific autoantigens and immunologic mechanisms involved in the pathogenesis of experimental and clinical uveitis. Recent investigations here have developed an experimental model of sympathetic ophthalmia by sensitization of guinea pigs to purified homologous retina S antigen. In order to elucidate the immune mechanisms involved in disease development, we propose to define the roles of both humoral and cellular factors which are contributory to pathogenesis. With development of the model, we also have a purified antigen for use in clinical diagnostic approaches and an experimental tool for investigation of therapeutic approaches based upon modulation of responses and immunosuppression. In related studies, we also propose to isolate and define the role of at least two additional retina organ specific antigens in pathogenesis of experimental uveitis. Results are expected to distinguish those antigens with experimental pathogenic capability and direct attention to those which may be of interest clinically.
NIH ExPorter
NIH ExPorter