Restoration of visual function by transplantation of optogenetically engineered photoreceptors [article]

Marcela Garita-Hernandez, Marusa Lampic, Antoine Chaffiol, Laure Guibbal, Fiona Routet, Tiago Santos-Ferreira, Giuliana Gagliardi, Sacha Reichman, Serge Picaud, Jose-Alain Sahel, Olivier Goureau, Marius Ader (+2 others)
2018 bioRxiv   pre-print
A major challenge in the treatment of retinal degenerative diseases, with the 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 a RPE-independent treatment approach, we introduced a hyperpolarizing microbial opsin into photoreceptor precursors from new-born mice, and transplanted them
more » ... ransplanted 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 behavioural tests. Subsequently, we generated cone photoreceptors from human induced pluripotent stem cells, 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.
doi:10.1101/399725 fatcat:ak3jd6rxlbeqbj5pw6dhd5c3ey