biostudies-literature00550Sengupta AAgence Nationale de la RechercheEuropean Research CouncilUniversité Pierre et Marie CurieCentre National de la Recherche ScientifiqueInstitut National de la Santé et de la Recherche Médicale1248-1264https://www.ebi.ac.uk/biostudies/studies/S-EPMC5090658biostudies-literatureUnknown8(11)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.EMBO molecular medicineRed-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina.PMC5090658ANR‐10‐LABX‐65309776Sahel JAMarre OForster VDuebel JDesrosiers MSengupta ALampic MPicaud SMace ECaplette RLin JYChaffiol ADalkara D55falseRed-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina.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.2016-01-01T00:00:00Z2016 Nov2024-11-13T17:52:40.015Z2019-03-27T02:28:02ZS-EPMC50906582767967110.15252/emmm.201505699