Age-related macular degeneration

Description

Age-related macular degeneration (AMD) causes vision loss due to photoreceptor (PR) degeneration, but disease models and therapies are missing. PR transplantation represents a promising treatment approach, but clinical translation remains a challenge. Our consortium aims to bridge two related research gaps: modeling of AMD pathology and therapy development (preventive and restorative). We developed a human retinal organoid (HRO) model with cellular and molecular AMD hallmarks in which PR degeneration occurs via cell extrusion, a pathology also described in AMD patients and correlating with ageing. PR extrusion mechanisms might offer targets to prevent AMD and to improve PR transplantation ? since both might share common and/or interrelated processes. For example, metabolic stress and inflammation, which are key in AMD, and known triggers of cell extrusion in other organs, might cause PR extrusion. Thus, the aims of the consortium are: (A) Decipher disease mechanisms by comparing our human and mouse AMD models, (B) determine function of inflammation (microglia) and metabolic changes, and (C) optimize PR transplantation in human AMD model. To achieve this, we will: 1. Optimize our platform for human PR transplantation into HROs, 2. identify regulators of AMD pathologies, and 3. modify potential regulators of PR extrusion to prevent pathogenesis and/or to stimulate PR transplant integration. Given our achievements, we will patent, publish and pursue towards clinical translation.