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
Vision is of key importance for humans and losing vision has a major effect on day-to-day life. Vision starts in the retina, where an image captured by photoreceptors is processed by retinal circuits built from more than hundred cell types. Information flows from the retina via the thalamus to a number of cortical areas. Despite the large number of cortical neurons involved in vision, most blinding diseases originate in the retina and are cell-type specific. Although the vertebrate retina has a conserved cellular architecture, only a few animal models of visual diseases reproduce the pathology found in humans. Therefore, there is a major need for understanding the healthy and the disease-affected human retina.
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.
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 recorded light evoked activity from donor human retinas, including recordings from ganglion cells and bipolar cells. We determined the gene expression patterns of different human retinal cell types.
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 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 provided the first recordings of light evoked activity from 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.
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.