Sengupta, A;
Chaffiol, A;
Macé, E;
Caplette, R;
Desrosiers, M;
Lampič, M;
Forster, V;
... Duebel, J; + view all
(2016)
Red-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina.
EMBO Molecular Medicine
, 8
(11)
pp. 1248-1264.
10.15252/emmm.201505699.
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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.
| Type: | Article |
|---|---|
| Title: | Red-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.15252/emmm.201505699 |
| Publisher version: | https://doi.org/10.15252/emmm.201505699 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Channelrhodopsin, optogenetics, primate, retina, vision restoration, Animals, Dependovirus, Genetic Therapy, Genetic Vectors, Humans, Lentivirus, Light, Macaca, Mice, Phototherapy, Retina, Retinal Degeneration, Rhodopsin, Transduction, Genetic, Treatment Outcome |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10053669 |
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