Akiba Ryutaro, Matsuyama Take, Takahashi Masayo, Mandai Michiko
Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, Riken.
Nihon Yakurigaku Zasshi. 2020;155(2):93-98. doi: 10.1254/fpj.19124.
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 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 in human clinical trial using iPSC derived retina for RP.
视网膜色素变性（RP）是一组涉及光感受器丧失的遗传性疾病。目前尚无针对RP的确立治疗方法，它现在是日本第二大致盲原因。先前使用人胎儿视网膜移植的临床研究表明视力有一定程度的功能恢复，但由于使用胎儿组织存在伦理问题，它并未成为标准疗法。2006年诱导多能干细胞（iPSC）的发明以及从ES/iPS细胞建立视网膜类器官诱导方案，为无伦理问题的RP细胞治疗铺平了道路。我们的团队已经表明，小鼠iPSC衍生的视网膜在视网膜下移植到终末期视网膜变性模型小鼠后能够存活并成熟。此外，人ESC衍生的视网膜在视网膜变性猴模型中存活并成熟。最近，我们建立了一种用于光感受器突触的定性和定量评估工具QUANTOS，并表明小鼠iPSC衍生视网膜中的光感受器在移植后可随时间形成光感受器突触。我们现在正朝着使用iPSC衍生视网膜治疗RP的人体临床试验迈进。
