TRANSPLANTATION OF RETINAL-PIGMENT EPITHELIAL-CELLS AND IMMUNE-RESPONSE IN THE SUBRETINAL SPACE

PURPOSE. TO evaluate the fate of retinal pigment epithelial cell (RPE) allografts in the subretinal space. METHODS. Transplantation was perf ormed in Royal College of Surgeons (RCS) rats. Two rat strains, ED IX and LES, which have incompatible major histocompatibility complex (MHC ) haplotypes, were selected as healthy RPE donors. :Transplantation wa s performed when recipients were 19 to 21 days old. Host systemic immu nity was enhanced by challenge with donor spleen cells 2 weeks after R PE transplantation. Central subjects were administered injections of s aline or host spleen cells. The animals were killed at 3 or 5 months o f age. The extent of photoreceptor rescue was determined by counting t he maximum layers of surviving photoreceptor nuclei in histologic sect ions. Reverse transcription-polymerase chain reaction analysis of the grafts was performed with host-and donor-specific printers. RESULTS. D espite the absence of acute immune rejection, chronic rejection occurr ed and was evidenced by an increased loss of photoreceptor cells in im munologically challenged RCS rats. Grafts with disparity at MHC class I and class II lost their ability to rescue photoreceptor cells more r eadily than did grafts with disparity at MHC class II alone. Furthermo re, the donor RPE cells that were normally MHC class II-negative expre ssed MHC class II mRNA in the subretinal space after transplantation. CONCLUSIONS. Systemic immunity appeared to exert a slow but significan t influence in the subretinal space. Therefore, in planning future tri als involving human subjects, the immunologically privileged status of the subretinal space should be regarded as imperfect.