[Toward establishment of regenerative cell therapy for retinitis pigmentosa using iPS cell derived retinal sheet]

Retinitis pigmentosa (RP) is a group of hereditary diseases that involve loss of photoreceptors. There has been no established treatment for RP, and it is now the 2^nd leading cause of blindness in Japan. Previous clinical researches using human fetal retina transplantation suggested some functional recovery in vision, but it did not become a standard therapy because of ethical concerns for using fetus tissues. Invention of induced pluripotent stem cells (iPSC) in 2006 and the establishment of retinal organoids induction protocol from ES/iPS cells have paved a way of cell therapy for RP without ethical concerns. Our team has shown that mouse iPSC derived retinas can survive and mature after subretinal transplantation to the end-stage retinal degeneration model mice. Further, human ESC derived retinas survived and matured in retinal degeneration monkey models. Recently, we have established a qualitative and quantitative evaluation tool for photoreceptor synapses, QUANTOS, and showed that photoreceptors in mouse iPSC derived retina can form photoreceptor synapses in a time dependent manner after transplantation. We are now moving toward 1^st in human clinical trial using iPSC derived retina for RP.