Restoration of visual function by transplantation of optogenetically engineered photoreceptors

Overview & Synopsis

A major challenge in treatment of retinal degenerative diseases with transplantation of replacement photoreceptors is the difficulty in inducing the grafted cells to grow and maintain light-sensitive outer segments in the host retina, which depends on proper interaction with the underlying retinal pigment epithelium (RPE). For an RPE-independent treatment approach, we introduced a hyperpolarizing microbial opsin into photoreceptor precursors from newborn mice, and transplanted them into blind mice lacking the photoreceptor layer. These optogenetically transformed photoreceptors were light responsive and their transplantation lead to the recovery of visual function, as shown by ganglion cell recordings and behavioral tests. Subsequently, we generated cone photoreceptors from human induced pluripotent stem cells (hiPSCs), expressing the chloride pump Jaws. After transplantation into blind mice, we observed light-driven responses at the photoreceptor and ganglion cell level. These results demonstrate that structural and functional retinal repair is possible by combining stem cell therapy and optogenetics.