Periodic Reporting for period 2 - HURET (The human retina at single cell resolution: functional architecture, disease mechanism and therapy development)
Reporting period: 2022-05-01 to 2023-10-31
In a recent survey, blindness was ranked as the worst human condition, ahead of Alzheimer disease or cancer. This heightened emphasis on vision and its diseases is likely the consequence of modern living, where most forms of information exchange involve the use of visual devices. Given that the proportion of people with visual impairment or blindness is growing exponentially with the increased mean age of the population, diseases of vision will continue to be a major problem for society.
In this worked we first aimed to describe the functional diversity as well as the function of ganglion cell types and their circuits in the human retina. Second, we aimed to reveal mechanisms of retinal cell-type vulnerability in the human retina. Third, we aimed to provide proof of principle for cell type-targeted near infrared vision restoration in the human retina. Taken together, this study provides insights into the structure, function, and mechanisms of disease of the cell types in the human visual system and investigates a new approach to restore vision in patients with blinding diseases.
We performed a compound screen on ~20’000 human retinal organoids to search for compounds that increase cone survival and those that damage cones. We isolated set of cone-saving and cone-damaging compounds.
We provided proof of principle for cone-targeted near infrared vision restoration in human retinas.
We performed the first cell type targeted compound screen in human retinal organoids.
We described the first method to restore visual activity using near-infrared light.
Together with Jose Sahel we reported the first blind patient who partially regained vision after optogenetic therapy.