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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-01-27

AUTHORS

Gregory Gauvain, Himanshu Akolkar, Antoine Chaffiol, Fabrice Arcizet, Mina A. Khoei, Mélissa Desrosiers, Céline Jaillard, Romain Caplette, Olivier Marre, Stéphane Bertin, Claire-Maelle Fovet, Joanna Demilly, Valérie Forster, Elena Brazhnikova, Philippe Hantraye, Pierre Pouget, Anne Douar, Didier Pruneau, Joël Chavas, José-Alain Sahel, Deniz Dalkara, Jens Duebel, Ryad Benosman, Serge Picaud

ABSTRACT

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 1015 photons.cm-2.s-1. Vector doses of 5 × 1010 and 5 × 1011 vg/eye transfected up to 7000 RGCs/mm2 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. More... »

PAGES

125

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s42003-020-01594-w

DOI

http://dx.doi.org/10.1038/s42003-020-01594-w

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1134917167

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33504896


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