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Red-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina

Citation

Sengupta, A and Chaffiol, A and Mace, E and Caplette, R and Desrosiers, M and Lampic, M and Forster, V and Marre, O and Lin, JY and Sahel, J-A and Picaud, S and Dalkara, D and Duebel, J, Red-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina, EMBO Molecular Medicine, 8, (11) pp. 1248-1264. ISSN 1757-4676 (2016) [Refereed Article]


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Copyright 2016 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.15252/emmm.201505699

Abstract

Targeting 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.

Item Details

Item Type:Refereed Article
Keywords:channelrhodopsin, optogenetics, primate, retina, vision restoration
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Lin, JY (Dr John Lin)
ID Code:114100
Year Published:2016
Web of Science® Times Cited:23
Deposited By:Medicine (Discipline)
Deposited On:2017-02-06
Last Modified:2018-03-08
Downloads:20 View Download Statistics

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