Optogenetic therapy: high spatiotemporal resolution and pattern discrimination compatible with vision restoration in non-human primates.

Autor: Gauvain G; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France. gregory.gauvain@inserm.fr., Akolkar H; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France.; Department of Ophthalmology, University Pittsburgh Medical Center, Pittsburgh, PA, USA., Chaffiol A; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France., Arcizet F; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France., Khoei MA; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France., Desrosiers M; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France., Jaillard C; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France., Caplette R; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France., Marre O; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France., Bertin S; CHNO des Quinze-Vingts, INSERM-DGOS CIC 1423, 28 rue de Charenton, F-75012, Paris, France., Fovet CM; Département des Sciences du Vivant (DSV), MIRcen, Institut d'imagerie Biomédicale (I2BM), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), 92260, Fontenay-aux-Roses, France., Demilly J; Département des Sciences du Vivant (DSV), MIRcen, Institut d'imagerie Biomédicale (I2BM), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), 92260, Fontenay-aux-Roses, France., Forster V; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France., Brazhnikova E; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France., Hantraye P; Département des Sciences du Vivant (DSV), MIRcen, Institut d'imagerie Biomédicale (I2BM), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), 92260, Fontenay-aux-Roses, France., Pouget P; ICM, UMRS 1127 UPMC - U 1127 INSERM - UMR 7225 CNRS, Paris, France., Douar A; Gensight Biologics, 74 rue du faubourg Saint Antoine, F-75012, Paris, France., Pruneau D; Gensight Biologics, 74 rue du faubourg Saint Antoine, F-75012, Paris, France., Chavas J; Gensight Biologics, 74 rue du faubourg Saint Antoine, F-75012, Paris, France., Sahel JA; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France.; Department of Ophthalmology, University Pittsburgh Medical Center, Pittsburgh, PA, USA.; CHNO des Quinze-Vingts, INSERM-DGOS CIC 1423, 28 rue de Charenton, F-75012, Paris, France., Dalkara D; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France., Duebel J; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France., Benosman R; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France.; Department of Ophthalmology, University Pittsburgh Medical Center, Pittsburgh, PA, USA., Picaud S; Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France. serge.picaud@inserm.fr.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2021 Jan 27; Vol. 4 (1), pp. 125. Date of Electronic Publication: 2021 Jan 27.
DOI: 10.1038/s42003-020-01594-w
Abstrakt: Vision restoration is an ideal medical application for optogenetics, because the eye provides direct optical access to the retina for stimulation. Optogenetic therapy could be used for diseases involving photoreceptor degeneration, such as retinitis pigmentosa or age-related macular degeneration. We describe here the selection, in non-human primates, of a specific optogenetic construct currently tested in a clinical trial. We used the microbial opsin ChrimsonR, and showed that the AAV2.7m8 vector had a higher transfection efficiency than AAV2 in retinal ganglion cells (RGCs) and that ChrimsonR fused to tdTomato (ChR-tdT) was expressed more efficiently than ChrimsonR. Light at 600 nm activated RGCs transfected with AAV2.7m8 ChR-tdT, from an irradiance of 10 15 photons.cm -2 .s -1 . Vector doses of 5 × 10 10 and 5 × 10 11 vg/eye transfected up to 7000 RGCs/mm 2 in the perifovea, with no significant immune reaction. We recorded RGC responses from a stimulus duration of 1 ms upwards. When using the recorded activity to decode stimulus information, we obtained an estimated visual acuity of 20/249, above the level of legal blindness (20/400). These results lay the groundwork for the ongoing clinical trial with the AAV2.7m8 - ChR-tdT vector for vision restoration in patients with retinitis pigmentosa.
Databáze: MEDLINE
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