Light allows vision but it can also trigger blindness. Light is an identified risk factor for the induction of age-related macular degeneration (AMD). In AMD, blindness results from the loss of photoreceptors, but blindness can also occur from the degeneration of retinal ganglion cells forming the optic nerve as in glaucoma.
We have defined the most toxic wavelengths for retinal cells while investigating novel strategies for restoring vision in blind patients.
Using 10 nm bands of wavelengths, we demonstrated that blue violet light is the most toxic light for photoreceptors and retinal epithelial cells. Paris summer sunlight is already in the damaging range. After evaluating an infrared photovoltaic prosthesis in non-human primates, the PRIMA prosthesis reached clinical trials in blind patients affected by AMD. They recovered a visual acuity close to 1/20 allowing word reading. To reach a cellular resolution, we introduced the microbial opsin, ChrimsonR-tdTomato, in retinal ganglion cells. This strategy provided a high spatial resolution with possible video rate activation of the non-human primate retina. Patients injected with the AAV2-7m8 ChrimsonR-tdTomato were able to grasp and count objects on a table. For cortical visual restoration, ultrasounds can penetrate deeply into the brain by contrast to light. Therefore, we proposed to render cortical neurons sensitive to ultrasounds by expressing the mechanosensitive ionic channel MscL via gene therapy. We provided the proof of concept on rodents that this sonogenetic therapy offers a spatial and a temporal resolution compatible with visual restoration.
In conclusion, we should protect ourselves from the toxic blue violet light. Clinical trials have demonstrated the efficacy of the photovoltaic PRIMA retinal prothesis in blind AMD patients while optogenetic therapy (GS030) was shown to restore partial vision in blind patients affected by retinitis pigmentosa. Sonogenetic therapy offers great hopes for patients with optic nerve atrophy.