Photoreceptor repair in response to RPE transplants in RCS rats: Outer segment regeneration

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Abstract
Purpose. We have previously shown that transplants of normal rat neonatal RPE cells rescued photoreceptor cells in retinas of Royal College of Surgeons (RCS) dystrophic rats for up to one year. In this study, we investigated the photoreceptor rescue effects in RCS rats within the first three weeks following transplantation in an attempt to determine if RPE transplants initiate repair mechanisms, specifically outer segment (OS) regeneration. Methods. Freshly isolated RPE cells from neonatal pigmented Long Evans rats were transplanted into the subretinal space of 22-23 day-old RCS rats using a transscleral approach. For controls, vehicle was similarly injected. Results. When analyzed at 10 days post-transplantation, long inner segments were observed with short buds of outer segment growth in the area of the RPE-cell transplants. The outer segments were of insufficient length to be measured at 10 days, but by 14 and 21 days, OS were 2.02 +/- 0.32 mu m and 18.80 +/- 2.78 mu m, respectively. In vehicle-injected retinas from 10 to 21 days postsurgery, outer segments were not observed and the inner segments were three-fold shorter than in RPE-transplanted retinas. At 10 days post-transplantation, most RPE cells were seen in the subretinal space, but a few had attached to Bruch's membrane; however, by 21 days, many of the transplanted RPE cells had attached to Bruchs membrane, although a few were found free in the subretinal space. Conclusions. This study has shown that transplants of normal rat neonatal RPE cells have the capacity to support not only photoreceptor cell survival but also initiate early repair mechanisms as exhibited by outer segment regeneration in RCS retinas. These results also conclusively show the important role that the RPE plays in outer segment growth and maturation.