The retina is a well-known immune-privileged tissue in the eye. Gene therapy and transgenic strategies have been taken to explore the relationship between the immune system and retinal antigens. Retroviruses were used to express retina-specific antigens or fragments systemically, leading to an antigen-specific loss of susceptibility to autoimmune disease. Transgenic strategies used a neo self-antigen, ß- galactosidase, or a known retinal antigen, interphotoreceptor retinoid-binding protein, to show that immune recognition of antigen by mice, which express solely in the retina, is not detectably different than that of mice that don't express this antigen. Together, these studies show that antigens expressed solely in the retina do not appear to be seen by the immune system, demonstrating that sequestration contributes to the lack of antigen recognition and absence of tolerance. Provision of these antigens outside of the retina provides the opportunity for development of peripheral tolerance, protection from autoimmunity, and potential therapies.