Transplantation of human induced pluripotent stem cell-derived retinal tissue in primate models of retinal degeneration with perimetric analysis

Abstract

Purpose : Retinal transplantation therapy for retinitis pigmentosa is increasingly of interest. We investigated the competency of human induced pluripotent stem cell-derived retinal tissue (hiPSC-retina) following transplantation into primate model of retinal degeneration. We also tried perimetric studies with an eye of retinal degeneration model in purpose of evaluating functional restoration after retinal transplantation.

Methods : hiPSC-retina of differentiation day (DD) 63 was transplanted into the laser photocoagulated retina of a cynomolgus monkey, and the monkey was sacrificed for immunohistological analysis at graft age of DD282 following in vivo imaging. A rhesus monkey was trained to perform perimetric analysis, and visual field defect was investigated after focal laser photocoagulation.

Results : OCT imaging demonstrated the presence of graft retina-like sheets in regions where the host ONL was substantially degenerated. Photoreceptors in the graft were observed to form rosette-like structures. FA revealed no evidence of rejection. All the rosettes were positive for recoverin, rhodopsin, and cone opsins, indicating terminal photoreceptor maturation. No proliferating (Ki67-positive) cells were observed in rosettes. Photoreceptor cells, co-expressing human markers and recoverin, were found to be in contact with host bipolar dendrites. We next successfully detected focal visual field loss in the corresponding area after laser photocoagulation, which was never observed before injury. Transplantation of hiPSC-retina was safely done in the photocoagulated area.

Conclusions : We demonstrated that the graft could survive, mature, and possibly integrate with host bipolar cells in the eye of the monkey model. With successful detection of visual field defect in the photoreceptor degenerating retina and transplantation within the degeneration site, we intend to monitor light perception of the graft area.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.