Autoimmunity may contribute to retinal degeneration. The studies examined the evolution of autoimmune responses against retina in naïve dystrophic RCS rats over the course of retinal degeneration. We showed that anti-retinal autoantibodies and T cells are generated in response to the availability of antigenic material released from dying photoreceptor cells during retinal degeneration but with distinctive activation trends. Passive transfer of anti-retinal antibodies enhanced disease progression by disrupting the BRB, upregulating MCP-1, attracting blood macrophages into retina, and augmenting apoptotic photoreceptor cell death. Our findings directly link anti-retinal autoantibodies to activated macrophage entry and their possible role in neurodegeneration.

Successful therapies for autoimmune uveitis must specifically inhibit pathogenic inflammation without inducing generalized immunosuppression. RTLs can offer such an option. The single retina-specific RTLs may have a value as potential immunotherapeutic drug for human autoimmune uveitis because they effectively prevent disease induced by multiple T cell specificities.