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

Published on Nov 1, 2016in Embo Molecular Medicine8.821
· DOI :10.15252/EMMM.201505699
Abhishek Sengupta2
Estimated H-index: 2
(French Institute of Health and Medical Research),
Antoine Chaffiol12
Estimated H-index: 12
(Vision Institute)
+ 10 AuthorsJens Duebel18
Estimated H-index: 18
(French Institute of Health and Medical Research)
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 post-mortem human retina.
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