Maintenance of opsin and S-antigen gene expression in RCS dystrophic rats following RPE transplantation

Abstract

The effects of retinal pigment epithelium (RPE) transplantation in rescuing photoreceptor cells (PRC) were studied in RCS rats bearing the rdy mutation. RPE preparations from Long-Evans rats were transplanted into the subretinal space of post-natal (P) 17–19-day-old RCS rats. Age-matched RCS animals in the control group received injections of the transplantation vehicle buffer alone. The animals were killed at various post-natal ages after RPE transplantation. Immunocytochemical studies using antibodies to opsin and S-antigen indicated intact photoreceptor cells in the transplanted retinas. In contrast age-matched sham-injected animals did not show any rescue of photoreceptor cells at P90. Single RPE transplantation of 60 000 cells in each eye resulted in restoration of near normal mRNA levels for opsin, and S-antigen proteins. Comparisons of mRNA levels of two visual proteins using cDNA probes demonstrated a therapeutic effect of RPE transplantation in preventing a progressive decline in mRNA levels due to retinal degeneration. In contrast, P109 sham-injected controls showed no detectable mRNA levels for these proteins. In vitro protein synthesis in RPE-transplanted retinas implied further competence of these retinas. These data suggest that RPE transplantation not only rescues photoreceptors from degeneration, but more importantly, it allows normal transcription and translation in these cells rendering them capable of participating in the visual and signal transduction cascade.