Transplantation of A Genetically Engineered Rat Retinal Pigment Epithelial Cell Line (LD 7.4) Preserves Retinal Function and Morphology in RCS Rats

Abstract

Abstract: : Purpose: To develop an allograft model of retinal pigment epithelial cell (RPE) transplantation to the sub-retinal space of the Royal College of Surgeons (RCS) rat using a genetically engineered RPE cell line (LD 7.4) to prevent retinal degeneration. Methods: A cell line was engineered by immortalization of primary cultures of PVG derived RPE (LD7.4). We transplanted these cells into the RCS rat subretinal space and sham operated animals were used for comparison. No animals were placed on immunosuppression. Eyes were retrieved at early time points to assess cellular (macrophage and T-lymphocyte) reactions and grafted cell survival. Animals underwent primary behavioral testing (head tracking assessment) and collicular threshold response mapping at four or five months and all were retrieved for histology. Threshold maps and photoreceptor rescue were compared. Results:In immunosuppressed animals a marked cellular reaction to the grafts was observed and there was a diminution in graft cell survival in the immediate post graft period. There was significant functional rescue in animals with transplants demonstrated by greater head tracking ability and threshold retinal sensitivity compared with sham. Greater histological rescue was seen in the transplanted group and the amount of rescue correlated well with sensitivity maps. The beneficial effects observed deteriorated over time and mechanisms responsible for this attenuation are currently being investigated. Conclusion: Use of a genetically engineered allogeneic cell line provides a valid model of RPE allograft transplant strategies. There was a significant delay in functional and anatomical degeneration in the RCS rat; however this delay was not indefinite.

Keywords: 607 transplantation • 567 retinal pigment epithelium • 518 photoreceptors: visual performance