Effects of RPE Age and Culture Conditions on Support of Photoreceptor Cell Survival in Transplanted RCS Dystrophic Rats

Abstract

This study assessed the effects of transplants of freshly isolated or cultured (ie. passaged) retinal pigment epithelial (RPE) cells from neonatal and adult normal and RCS pigmented dystrophic rats on photoreceptor cell survival in retinas of 22-26-day-old pink-eyed RCS dystrophic rats. We determined that retinas of 2-month-old RCS rats transplanted at 26 days with RPE cells of adult RCS rats did not support photoreceptor cell survival above that seen in sham or nontreated control RCS retinas, as outer nuclear layer (ONL) thicknesses were not significantly different (10-0± 1·31 μm, 11·7±4·04 μm and 9·42 ±1·88 μm. respectively). Surprisingly, in this same transplant group, RPE transplants from neonatal RCS dystrophic rats were able to promote photoreceptor cell survival similar to that seen in transplants of neonatal Long Evans rats, as evidenced by similar ONL thicknesses (34·4±3·16 μm and 33·6±6·03 μm, respectively), but the rescue effect quickly diminished. However, in retinas of 22-26-day-old RCS rats transplanted with RPE cells from adult Long Evans rats, the level of photoreceptor cell rescue was approximately 48% (ONL: 19·6± 2·79 μm), when compared to retinas transplanted with RPE cells from neonatal Long Evans rats, but significantly greater than that caused by transplants of RPE cells from adult RCS rats. In a second transplant study, retinas of 3-month-old RCS rats transplanted at postnatal days 22-23 with freshly isolated neonatal RPE cells had an ONL thickness of 31·5±3·5 μm, while those retinas transplanted with first- and third-passaged neonatal RPE cells had an ONL which measured 15·5±3·55 μm and 9·99±3·67 μm, respectively. In contrast retinas of 22-23-day-old RCS rats transplanted with freshly isolated and third-passaged RPE cells from 17-month-old Long Evans rats had ONL thicknesses of 5·89±0·65 μm and 6·48±2·52 μm, respectively, neither of which was significantly greater than the ONL thickness in sham-injected retinas (6·07±1·31 μm). In conclusion, this study demonstrated a significant age-related decline in the ability of transplants of adult rat RPE cells and transplants of passaged RPE cells to support photoreceptor cell survival in retinas of RCS rats.