Project: HUMAN ORGANOID SYSTEM BASED THERAPY DISCOVERY AND DEVELOPMENT FOR AGE-RELATED MACULAR DEGENERATION

Acronym	ReDiMoAMD (Reference Number: NEURON-083)
Duration	01/10/2021 - 30/09/2024
Project Topic	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.
Network	NEURON Cofund
Call	Call for Proposals for Transnational Research Projects on Sensory Disorders

Project partner

Number	Name	Role	Country
1	TU Dresden	Coordinator	Germany
2	TU Dresden	Partner	Germany
3	INSERM UMRS 968	Partner	France
4	University of Toronto	Partner	Canada
5	ETH Zürich	Partner	Switzerland