Immunologic consequences of intraocular implantation of retinal pigment epithelial allografts

Immune rejection is a major concern for potential therapeutic RPE transplantation. The purpose of this study is to determine the pattern and consequences of immune responses to intraocular retinal pigment epithelial (RPE) allografts. RPE allografts which derive from C57BL/6 newborn mice were implanted into the subretinal space (SR), anterior chamber (AC) and subconjunctival space (SCon) of the eyes of adult BALB/c mice. After implantation, clinical, histological and immunological examinations were conducted. Results revealed that RPE allografts implanted into SR and AC had a prolonged survival which is associated with a suppression of donor-specific delayed hypersensitivity (DH) for at least 12 days. In contrast, similar RPE grafts implanted into the SCon induced conventional DH and grafts were rejected. Moreover, previously healthy intraocular RPE grafts were rejected 2 weeks after a donor-specific challenge and rejection was accomplished with extensive cell infiltration which subsequently damaged intraocular tissue of the host eye. These results suggested that intraocular RPE allografts enjoyed immune privilege and induced a down-regulation of immune responses. However, this privilege is not absolute and static--DH was able to emerge and grafts were rejected in a cell-mediated fashion.