Red‐shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina
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 safet...
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| Format: | Article |
| Language: | English |
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Springer Nature
2016-09-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201505699 |
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| author | Abhishek Sengupta Antoine Chaffiol Emilie Macé Romain Caplette Mélissa Desrosiers Maruša Lampič Valérie Forster Olivier Marre John Y Lin José‐Alain Sahel Serge Picaud Deniz Dalkara Jens Duebel |
| author_facet | Abhishek Sengupta Antoine Chaffiol Emilie Macé Romain Caplette Mélissa Desrosiers Maruša Lampič Valérie Forster Olivier Marre John Y Lin José‐Alain Sahel Serge Picaud Deniz Dalkara Jens Duebel |
| author_sort | Abhishek Sengupta |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-754898926dc74e3a8b3a6c9af06db69b |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2016-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-754898926dc74e3a8b3a6c9af06db69b2025-08-20T03:43:30ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842016-09-018111248126410.15252/emmm.201505699Red‐shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retinaAbhishek Sengupta0Antoine Chaffiol1Emilie Macé2Romain Caplette3Mélissa Desrosiers4Maruša Lampič5Valérie Forster6Olivier Marre7John Y Lin8José‐Alain Sahel9Serge Picaud10Deniz Dalkara11Jens Duebel12INSERM, U968INSERM, U968INSERM, U968INSERM, U968INSERM, U968INSERM, U968INSERM, U968INSERM, U968School of Medicine, University of TasmaniaINSERM, U968INSERM, U968INSERM, U968INSERM, U968Abstract 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.https://doi.org/10.15252/emmm.201505699channelrhodopsinoptogeneticsprimateretinavision restoration |
| spellingShingle | Abhishek Sengupta Antoine Chaffiol Emilie Macé Romain Caplette Mélissa Desrosiers Maruša Lampič Valérie Forster Olivier Marre John Y Lin José‐Alain Sahel Serge Picaud Deniz Dalkara Jens Duebel Red‐shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina EMBO Molecular Medicine channelrhodopsin optogenetics primate retina vision restoration |
| title | Red‐shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina |
| title_full | Red‐shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina |
| title_fullStr | Red‐shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina |
| title_full_unstemmed | Red‐shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina |
| title_short | Red‐shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina |
| title_sort | red shifted channelrhodopsin stimulation restores light responses in blind mice macaque retina and human retina |
| topic | channelrhodopsin optogenetics primate retina vision restoration |
| url | https://doi.org/10.15252/emmm.201505699 |
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