E-resources
-
Sengupta, Abhishek; Chaffiol, Antoine; Macé, Emilie; Caplette, Romain; Desrosiers, Mélissa; Lampič, Maruša; Forster, Valérie; Marre, Olivier; Lin, John Y; Sahel, José‐Alain; Picaud, Serge; Dalkara, Deniz; Duebel, Jens
EMBO molecular medicine, November 2016, Volume: 8, Issue: 11Journal Article
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. Synopsis A red‐shifted channelrhodopsin (ReaChR) was targeted to retinal ganglion cells using three models in parallel: mouse, macaque, and human. Safe orange illumination was able to trigger light responses in all three systems. The red‐shifted channelrhodopsin ReaChR restored light responses at the retinal, cortical, and behavioral levels in blind rd1 mice, using light intensities below the safety limit for the human retina. Optogenetic light responses were demonstrated in explanted postmortem macaque and human retina, infected ex vivo with viral vectors encoding ReaChR. The study presents the first electrophysiological recordings of optogenetic light responses in ganglion cells obtained directly from the human fovea as well as the far peripheral human retina. A red‐shifted channelrhodopsin (ReaChR) was targeted to retinal ganglion cells using three models in parallel: mouse, macaque, and human. Safe orange illumination was able to trigger light responses in all three systems.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.