Xenotransplantation of retinal pigment epithelial cells into RCS rats

Purpose: Successful engraftment of retinal pigment epithelial cells (RPE) to treat RPE-related retinopathy will depend, at least in part, on controlling the immune response. In order to understand this process we evaluated the fate of RPE xenografts in the subretinal space, anterior chamber, and subcutis of nonimmunosuppressed Royal College of Surgeons rats. Methods: Freshly isolated adult porcine RPE cells were used as xenografts and implanted when recipients were 17 to 21 days old. The extent of photoreceptor rescue by subretinal transplants was determined by counting the maximum layers of surviving photoreceptor nuclei in histologic sections. Cellular immune response was evaluated by immunohistochemistry. Results: Compared to non- or sham-injected eyes, subretinal xenografts in RPE-transplanted eyes were able to induce a dramatic rescue effect (P <. 01). However, the effect was not absolute and photoreceptor cell degeneration was only delayed. Xenografts both in the anterior chamber and in the subcutaneous tissue led to an inflammatory cellular infiltration. Conclusion: RPE xenografts in subcutaneous space and in the anterior chamber are rejected by a delayed but vigorous inflammatory cell infiltration. Subretinal RPE xenografts are protected from a strong cellular rejection, but seem to undergo a slow functional deterioration, reflected by a decline in their capability to rescue adjacent photoreceptors.