Project 3 - Retina organoids as models for assessing pathomechanisms and effects of novel treatments inn retinal disorders

Organoids—cell assemblies grown from stem cells in a Petri dish—replicate human organ cell types and morphology in unprecedented detail. Their accessibility and physiological relevance offer unprecedented insights into organ development, disease modeling, and therapy testing.

Retinal organoids, mimicking the light-sensitive eye tissue, contain all retinal cell types and genetic profiles, making them invaluable for studying diseases not well-replicated in animal models. This includes rare genetic disorders like Leber's hereditary optic neuropathy (LHON), which causes vision loss.

LHON, affecting young adults, results from mitochondrial DNA mutations impairing energy production, primarily harming retinal ganglion cells. Our team has contributed to clinical studies on idebenone (approved in the EU in 2015) and intravitreal gene therapy, yet many questions remain. Developing in vitro models of LHON-affected retina would be a breakthrough for understanding its mechanisms and testing new therapies.

No LHON organoid model exists yet. Our team is working on developing human retinal organoids as LHON disease models and use them to test gene therapies in collaboration with project partners. Combining our expertise in neural imaging and LHON gene therapy, we will characterize organoid function and evaluate novel treatments in living human retinal tissue. Ultimately, our models will advance understanding of LHON pathomechanisms and therapy development.