Abstract
Purpose :
Retinal pigment epithelium (RPE) plays an essential role in maintenance of photoreceptors. RPE disfunction may cause several diseases including retinitis pigmentosa, age-related macular degeneration, and pathologic myopia. Strategies for regenerative medicine are divided into autologous and allogeneic, somatic and stem cell-derived, an epithelial cell sheet and cell suspension. Iris pigment epithelium (IPE) is an alternative candidate because of relatively easy access for sampling. The purpose of this study is to prepare an IPE cell sheet for autologous implantation and evaluate neuroprotective effects in vivo.
Methods :
Using our own technology to produce an RPE cell sheet with Bruch’s membrane, a cell sheet of IPE cells, which were isolated from the iris and cultured, was prepared and implanted into the subretinal space of the right eye in 10 nude rats to evaluate possible adverse events histologically and in 13 royal college surgeons (RCS) rats under immunosuppression to assess neuroprotective efficacy. As the control group, only the sham surgery was performed in 10 nude rats and 10 RCS rats. At week 2, all of the right eyes of nude rats were enucleated to evaluate any adverse events histologically. In months 1 and 3, the right eyes of RCS rats were enucleated to assess both neuroprotective effects and any adverse events. To evaluate neuroprotective effects, the remaining outer nuclear layer (ONL) was graded from 1 to 5 (1: totally missing, 2: very slightly remaining, 3: slightly remaining, 4: moderately remaining, 5: largely remaining).
Results :
There were no adverse events both in and outside of the implanted site in nude rats and RCS rats. In the control group of RCS rats, 3 of 5 eyes in month 1 and all of 5 eyes in month 3 showed the totally missing ONL (grade 1). In contrast, the ONL was somewhat remaining in all of 8 eyes (in grades 2-4) in month 1 and 4 of 5 eyes (in grades 2 and 3) in month 3 in the group with the IPE cell sheet implantation.
Conclusions :
An IPE cell sheet implantation showed neuroprotective efficacy, suggesting the potential for regenerative medicine. We will plan to perform a phase I/IIa clinical study for regenerative medicine for diseases related to RPE dysfunction.
This is a 2021 ARVO Annual Meeting abstract.