Vision Restoration by Optogenetic Therapy and Developments Toward Sonogenetic Therapy

Abstract

After revolutionizing neuroscience, optogenetic therapy has entered successfully in clinical trials for restoring vision to blind people with degenerative eye diseases, such as retinitis pigmentosa. These clinical trials still have to evaluate the visual acuity achieved by patients and to determine if it reaches its theoretical limit extrapolated from ex vivo experiments. Different strategies are developed in parallel to reduce required light levels and improve information processing by targeting various cell types. For patients with vision loss due to optic atrophy, as in the case of glaucoma, optogenetic cortical stimulation is hampered by light absorption and scattering by the brain tissue. By contrast, ultrasound waves can diffuse widely through the dura mater and the brain tissue as indicated by ultrasound imaging. Based on our recent results in rodents, we propose the sonogenetic therapy relying on activation of the mechanosensitive channel as a very promising vision restoration strategy with a suitable spatiotemporal resolution. Genomic approaches may thus provide efficient brain machine interfaces for sight restoration.

Stage-Dependent Changes of Visual Function and Electrical Response of the Retina in the rd10 Mouse Model

“…The optogenetic approach, a different approach for vision restoration, has been proposed to overcome this limitation of electrical stimulation. The optogenetic approach using channel rhodopsin has been proposed for the selective activation of ON or OFF RGCs (Provansal et al, 2022). Optogenetic therapy using ChrimsonR in the living primate (Macaca fascicularis) is reported to restore characteristic RGC responses to patterned stimuli (McGregor et al, 2020(McGregor et al, , 2022.…”

Perceptual Learning: Policy Insights From Basic Research to Real-World Applications

“…Historically, some of the most prominent clinical targets for PL include amblyopia (Levi & Li, 2009), cortical visual impairments (Pollock et al, 2019;Saionz et al, 2021), refractive errors (Polat et al, 2012), low vision in youths (Nyquist et al, 2016) or older adults (DeLoss et al, 2014), and restoration of vision following removal of juvenile cataracts (Kalia et al, 2017). New challenges emerge as treatments for vision loss increasingly involve prosthetics-whether electronic versions applied to the retina (e.g., Argus II, Palanker, 2023) or cortex (cortical prostheses, Fine & Boynton, 2023), or through optogenetics (Provansal et al, 2022), gene therapies (Moraru et al, 2022), or stem cell transplantation (Öner, 2018). For instance, it is increasingly clear that new criteria and methods are needed to assess, and improve through training, the "ultra-low vision" created by these approaches (Ayton et al, 2020).…”

“…The specificity of PL has been explored for numerous stimulus dimensions (e.g., orientation, motion properties, depth, color, tone frequency, locations on the skin, etc.) and provide clues to where learning may be occurring in the brain (Sagi, 2011). These findings have important implications for visual rehabilitation as they inform how to target brain processes necessary to achieve desired patient outcomes (Das & Huxlin, 2010).…”

Untitled

“…Much progress has also been achieved using optogenetic technologies to restore vision in animals [285][286][287][288][289], and using chemical photoswitches [285] and retinal and brain implants [285,290]. Use of sonar technology to stimulate specific neuronal pathways to protect and enhance vision also holds great promise [291,292].…”