Optimal conditions for long-term photoreceptor cell rescue in RCS rats: the necessity for healthy RPE transplants.

Retinal pigment epithelial (RPE) cells from normal Long-Evans, healthy Royal College of Surgeons (RCS) pigmented congenic (rdy+p+) and RCS pigmented dystrophic rats were transplanted into retinas of RCS non-pigmented dystrophic rats at post-natal days 17 and 26 (P17 and P26). When examined at P60, rescued photoreceptor cells were found in all transplanted groups. In addition, a small, but significant increase in the outer nuclear layer (ONL) thickness was detected in retinas injected with vehicle (sham control); however, the ONL thickness was reduced to control levels by 3-5 months after injections in both the sham controls and the group grafted with RCS pigmented dystrophic RPE cells. Likewise, large volumes of vehicle were injected into the subretinal space resulting in no long lasting beneficial effects. Also, there was no significant difference between the ONL thickness in retinas grafted with RCS congenic RPE and those grafted with Long-Evans RPE. When donor RPE cells from Long-Evans rats at neonatal and adult stages were transplanted into P26 RCS hosts, photoreceptor cell rescue could be found; however, the younger RPE cells affected a better rescue than those derived from adult eyes. In addition, when RPE cells from 6- to 9-day-old Long-Evans rats were transplanted into retinas of RCS dystrophic rats at 10, 17 and 26 days, significant rescue of photoreceptor cells was observed. Of these transplantation times, day 17 appeared to affect the best rescue of photoreceptor cells up to 1 yr. In contrast, little or no rescue was observed in the retinas of those RCS dystrophic rats when RPE cell transplantation was performed at P38, P43 and P48. The photoreceptor cell rescue was also found to be dependent on the concentration of RPE cells injected, which was maximal at 60,000-120,000 cells microliters-1. These findings lead us to conclude that in order to affect long-term, up to 1 yr, rescue of photoreceptor cells in the RCS rat, young, healthy RPE cells are required and transplantation needs to be performed at early stages of the disease process.