A primary role for RPE transplants in the inhibition and regression of neovascularization in the RCS rat.

PURPOSE: Healthy retinal pigment epithelial (RPE) cell transplants in retinas of postnatal day 27 Royal College of Surgeons (RCS) rat are capable of preventing photoreceptor cell degeneration, inhibiting the degeneration of the retinal vascular bed and the subsequent neovascularization of the RPE that occurs in retinas injected with saline. In the present study, the authors have tested the hypothesis that RPE transplants might also prevent vascularization of the RPE layer in RCS retinas when photoreceptor cells either had just degenerated or, at 3 months, disappeared. METHOD: Retinas of 3- and 6 month-old RCS rats were injected with either healthy neonatal RPE cells or vehicle and were examined at 6 and 8 months, respectively. These retinas were studied using horseradish peroxidase visualization of the vasculature in retinal wholemount preparations and by light microscopy. RESULTS: The number of neovascular profiles in wholemount preparations of RCS retinas that had received healthy RPE transplants at 3 months and were analyzed at 6 months were significantly decreased when compared to sham-injected retinas of age-matched RCS rats, 2.09 +/- 0.94 and 15.28 +/- 1.34 profiles per mm2, respectively (P < 0.001). In addition, when comparing retinas transplanted or sham injected at 6 months and examined at 8 months, significantly fewer neovascular profiles were found in the transplant group, 9.32 +/- 1.02 and 15.42 +/- 0.84 profiles per mm2, respectively (P < 0.002). CONCLUSION: These data provide still further evidence for the role of healthy RPE in maintaining the homeostasis of the normal retinal vasculature in the retina of the RCS rat. The relationships between the RPE and the retinal vasculature are important when considering that alterations in the vascularization of the retina play a major role in some of the most sight-debilitating diseases, such as the wet form of age-related macular degeneration and proliferative diabetic retinopathy.

RPE transplants stabilize retinal vasculature and prevent neovascularization in the RCS rat.

Previous reports indicate that in the Royal College of Surgeons (RCS) rat a decline in the retinal vessel density accompanies the loss of the normal architecture of the deep bed. This begins at about three months with neovascularization that originates in the deep vessel bed and develops in the direction of the retinal pigment epithelial (RPE) cells by four months. A surgical technique has been developed recently for the transplantation of healthy RPE cells into the subretinal space of the RCS rat, resulting in the rescue of photoreceptor cells. This permits evaluation of the possibility that such transplants also protect the retinal vessels. We report for the first time: (1) the stabilization of the normal retinal vasculature by maintenance of the density and architecture of the deep vessel bed; and (2) prevention of neovascularization of the RPE by the surgical transplantation of healthy RPE cells into the subretinal space of the RCS rat. More specifically, we show a maintenance of the deep vessel bed density under the transplant in contrast to a significant reduction in the vessel density that had taken place in corresponding areas in nongrafted and sham injected controls at four months of age. The vessel density in the transplanted group is statistically different from the nongrafted and the sham injected groups. We also report a significant decline in the number of neovascularization profiles around the transplant site of the RPE-grafted RCS retina. We also note that the pathological changes in the vasculature of the RCS rat occur in a predictable central to peripheral gradient.

Transplantation to the diseased and damaged retina.

Retinas of Royal College of Surgeons (RCS) dystrophic rats undergo a dramatic loss of photoreceptor cells as a result of defective retinal pigment epithelial (RPE) cells. These retinas are therefore a valuable model in the investigation of the role of the RPE on photoreceptor-cell survival and development. Also, rat retinas damaged by excessive light serve as a suitable environment to study survival of transplanted photoreceptor cells. Even though photoreceptor cells are lost in these retinas, a normal inner retinal structure is retained. Both models have recently been used in successful RPE-cell and/or photoreceptor-cell transplantation studies designed to replace defective or lost cells due to retinal disease or damage. These new approaches in the field of retinal transplantation offer unique and novel opportunities for the development of possible therapeutic strategies in human eye disease, and for improving our understanding of the normal relationships between retinal cells.