Ontology type: schema:ScholarlyArticle Open Access: True
2019-10-04
AUTHORSMarcela Garita-Hernandez, Maruša Lampič, Antoine Chaffiol, Laure Guibbal, Fiona Routet, Tiago Santos-Ferreira, Sylvia Gasparini, Oliver Borsch, Giuliana Gagliardi, Sacha Reichman, Serge Picaud, José-Alain Sahel, Olivier Goureau, Marius Ader, Deniz Dalkara, Jens Duebel
ABSTRACTA 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). Here, for an RPE-independent treatment approach, we introduce a hyperpolarizing microbial opsin into photoreceptor precursors from newborn mice, and transplant them into blind mice lacking the photoreceptor layer. These optogenetically-transformed photoreceptors are light responsive and their transplantation leads to the recovery of visual function, as shown by ganglion cell recordings and behavioral tests. Subsequently, we generate cone photoreceptors from human induced pluripotent stem cells, expressing the chloride pump Jaws. After transplantation into blind mice, we observe light-driven responses at the photoreceptor and ganglion cell levels. These results demonstrate that structural and functional retinal repair is possible by combining stem cell therapy and optogenetics. More... »
PAGES4524
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