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Red-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina
journal contribution
posted on 2023-05-19, 01:23 authored by Sengupta, A, Chaffiol, A, Mace, E, Caplette, R, Desrosiers, M, Lampic, M, Forster, V, Marre, O, John LinJohn Lin, Sahel, J-A, Picaud, S, Dalkara, D, Duebel, JTargeting the photosensitive ion channel channelrhodopsin‐2 (ChR2) to the retinal circuitry downstream of photoreceptors holds promise in treating vision loss caused by retinal degeneration. However, the high intensity of blue light necessary to activate channelrhodopsin‐2 exceeds the safety threshold of retinal illumination because of its strong potential to induce photochemical damage. In contrast, the damage potential of red‐shifted light is vastly lower than that of blue light. Here, we show that a red‐shifted channelrhodopsin (ReaChR), delivered by AAV injections in blind rd1 mice, enables restoration of light responses at the retinal, cortical, and behavioral levels, using orange light at intensities below the safety threshold for the human retina. We further show that postmortem macaque retinae infected with AAV‐ReaChR can respond with spike trains to orange light at safe intensities. Finally, to directly address the question of translatability to human subjects, we demonstrate for the first time, AAV‐ and lentivirus‐mediated optogenetic spike responses in ganglion cells of the postmortem human retina.
Funding
National Institutes of Health
History
Publication title
EMBO Molecular MedicineVolume
8Issue
11Pagination
1248-1264ISSN
1757-4676Department/School
Tasmanian School of MedicinePublisher
Wiley-BlackwellPlace of publication
United KingdomRights statement
Copyright 2016 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/Repository Status
- Open