Immunological Aspects of Retinal Transplantation in Retinal Degeneration Rodents

Abstract

Retinal transplantation holds promise as a treatment for restoring vision in the eye which has been blinded by retinal degenerative disease. We have demonstrated that allogeneic retinal grafts implanted into intraocular spaces of normal eyes are immunologically privileged and this privilege is associated with an active downregulation of systemic immunity. Since the normal eye maintains an immune suppressive intraocular microenvironment, it is important to determine 1) whether the degenerative eye has a similar immunological microenvironment and 2) what impact donor-specific alloimmunity has on the function of retinal allografts. Two sets of experiments were carried out to answer these questions. First, we assayed the systemic immunity in C3H/Hen retinal degenerative mice which received an allogeneic neural retinal graft in either the anterior chamber or subretinal space. We found that these spaces are immunologically privileged sites for allogeneic retinal grafts and this privilege is accompanied by induction of suppression of donor-specific delayed hypersensitivity. Moreover, intraocular retinal allografts in C3H/Hen mice enjoyed a prolonged survival in these immunologically privileged sites. Our results from rd mice suggest that photoreceptor cells may not play an important role in maintaining an immune suppressive intraocular microenvironment. Second, we implanted normal retinal pigment epithelium (RPE) allografts into the subretinal space of retinal degenerative Royal College of Surgeons (RCS) rats and corneal electroretinographic (ERG)s were periodically recorded. The results indicate that the normal RPE allografts can rescue ERG function in the RCS recipients; however, after donor-specific immunization, the rescued ERG function was abolished. The property of immune privilege is maintained in the retinal degenerative eyes of RCS rats and rd mice. However, the emergence of systemic alloimmunity can overcome the immune privilege leading to an immunologically mediated impairment of retinal graft function. Thus, systemic immunity directed at donor-specific antigens is a major obstacle for functional retinal transplants.