Subretinal space and vitreous cavity as immunologically privileged sites for retinal allografts

Abstract

Purpose: Because immune rejection is likely to be a major barrier to successful retinal transplantation, it is important to determine whether immune privilege for allogeneic retinal grafts is a feature of the subretinal space and vitreous cavity.

Methods: Newborn neural retinas of C57BL/6 mice were implanted into the subretinal space, vitreous cavity, or subconjunctival space of eyes of adult BALB/c (disparate from C57BL/6 at major and minor histocompatibility loci). At postimplantation day 12, the recipients were evaluated for donor-specific delayed hypersensitivity and examined clinically and histologically for evidence of rejection.

Results: Newborn neural retinal allografts in the subconjunctival space were destroyed by postimplantation day 12 and these recipients displayed intense donor-specific delayed hypersensitivity. By contrast, grafts in the subretinal space and vitreous cavity at postimplantation day 12 were found to be well differentiated and with no evidence of inflammation; these recipients failed to display donor-specific delayed hypersensitivity. Moreover, their spleens contained regulatory T cells that suppressed donor-specific delayed hypersensitivity in naive syngeneic recipients.

Conclusions: Allogeneic newborn neural retinal grafts implanted in the subretinal space and vitreous cavity experience immune privilege and induce deviant immune responses resembling anterior chamber associated immune deviation.