RETINAL-PIGMENT EPITHELIAL-CELL TRANSPLANTATION IN RCS RATS - NORMAL METABOLISM IN RESCUED PHOTORECEPTORS

Photoreceptor cells in Royal College of Surgeons (RCS) rats with inherited retinal dystrophy can be rescued by the transplantation of normal, wild-type retinal pigment epithelial (RPE) cells, if done before photoreceptor cell death. In the present study, we have examined several metabolic features of rescued photoreceptors and transplanted RPE cells at 2.3-3.3 months after transplantation. Rescued photoreceptors with a structurally normal RPE interface showed a rod outer segment renewal rate similar to that of normal control rats of 2.2 μm day-1, as measured in autoradiograms. Rod outer segment disc shedding had values idistinguishable from those in normal controls, as measured by the number of phagosomes in the transplanted RPE cells both during the burst of disc shedding soon after the onset of light in the morning and during the middle of the light cycle when disc shedding is low. The interphotoreceptor matrix, which is synthesized by both photoreceptors and the RPE, was distributed normally in the regions where normal-appearing photoreceptors were present underlying normal, transplanted RPE cells. Thus, the rescued photoreceptors show normal metabolic rates and normal interactions with the RPE in each of the parameters examined. These findings, combined with the previous demonstration of opsin and Na+,K+-ATPase expression by the rescued photoreceptors, support our interpretation that the surviving, normal-appearing photoreceptors may function normally. Moreover, transplanation of normal RPE cells reversed pathological changes in the photoreceptors that had already occurred by the time of transplantation. Thus, it appears that if photoreceptors are capable of being rescued from cell death, at least some of their metabolic processes can be restored to normal levels by RPE cell transplantation. © 1992 Academic Press Limited.