Optogenetics & Vision: Interview with José-Alain Sahel

Article: How optogenetics has restored partial sight to a blind patient
Source: French National Center for Scientific Research, CNRS News
Published: June 23, 2021

Optogenetic response measured ex vivo in
a primate’s retina when presented with a symbol

Review of Optology earlier highlighted media coverage of a breakthrough story of the first clinical application of optogenetics to restore partial vision to a patient with terminal retinitis pigmentosa. An interview with the lead author of the study, José-Alain Sahel, in CNRS News  published this week takes a closer look at the research behind the scenes. Originally developed to study neural circuits of the brain, Sahel explains that a colleague's work applying the technique to the circuits of the retina prompted the idea to apply optogenetics to visual impairment. "This project required a lot of time and a great deal of tenacity," he revealed, "Although some of our colleagues thought this project was ludicrous, we held our course because we knew it made sense."

The challenges the team faced over the twelve years of the project included choosing the right proteins for the right type of cell, determining how they could be stimulated effectively, and developing visual rehabilitation protocols for patients. The researchers first explored injecting the proteins in bipolar cells, then in dormant photoreceptors. Though the latter experiments were successful at reactivating dormant cones, the proteins could not be sufficiently strongly expressed in these cells; work continues to be done in this area. They next turned their attention to retinal ganglion cells, which naturally react to light with melanopsin. Responsible for regulating circadian rhythm, melanopsin nonetheless responds too slowly for a strategy to stimulate vision. Sahel's team tested green fluorescent proteins before colleagues suggested channelrhodopsin (CrimsonR), which responds to low-energy amber light that they were looking for. The next obstacle was creating a projection system to stimulate the CrimsonR proteins. Because the application is rather unique, they set up a company, GenSight Biologics, to develop both the gene therapy and the equipment for its application. Finally, they collaborated with a platform called StreetLab to train the patients to use the light-stimulating goggles in real-life conditions. Sahel adds, "Our research is carried out in close collaboration with the patients, who play an active role in our work. We are convinced that in terms of rehabilitation, close ties between actors, developers and users are essential."

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