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EMBO Mol Med. 2016 Nov 2;8(11):1248-1264. doi: 10.15252/emmm.201505699. Print 2016 Nov.

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

Sengupta A1,2,3, Chaffiol A1,2,3, Macé E1,2,3, Caplette R1,2,3, Desrosiers M1,2,3, Lampič M1,2,3, Forster V1,2,3, Marre O1,2,3, Lin JY4, Sahel JA1,2,3,5, Picaud S1,2,3, Dalkara D6,2,3, Duebel J6,2,3.

Author information

1
INSERM U968, Paris, France.
2
Sorbonne Universités UPMC Univ Paris 06 UMR_S 968 Institut de la Vision, Paris, France.
3
CNRS UMR_7210, Paris, France.
4
School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
5
Hôpital des Quinze-Vingts, Paris, France.
6
INSERM U968, Paris, France jens.duebel@inserm.fr deniz.dalkara@gmail.com.

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.

KEYWORDS:

channelrhodopsin; optogenetics; primate; retina; vision restoration

PMID:
27679671
PMCID:
PMC5090658
DOI:
10.15252/emmm.201505699
[Indexed for MEDLINE]
Free PMC Article

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