Retinopathies

Degenerative retinal diseases are a leading cause of vision loss worldwide. In France, hereditary retinal disorders affect around 40,000 people, while age-related macular degeneration (AMD) affects more than 1.5 million. These progressive, severely disabling conditions damage retinal cells, particularly photoreceptors, and may ultimately lead to blindness. Retinitis pigmentosa is the most common group of inherited retinal degenerations; it is associated with variants in more than 70 genes (https://retnet.org/ ) and can impair vision at any age. Most retinal degenerative diseases remain incurable. Current options are limited to a small number of treatments, including Luxturna™ gene therapy for RPE65-related Leber congenital amaurosis, Syfovre™ for geographic atrophy secondary to AMD, and anti-VEGF therapies for wet AMD.

Building on these achievements, we are now developing more complex retinal tissues incorporating additional cell types and enhanced spatial organization through the use of micro-structured scaffolds (collaboration with C2N: Dr. Frédéric Hamouda and the team of Dr Didier Letourneur and Teresa Simon-Yarza (LVTS, INSERM UMRS1148)). The overall objective is to combine regenerative medicine, disease modelling and drug discovery to address retinal disorders for which curative treatments remain largely unavailable.

The team is jointly led by Prof. Christelle Monville and Dr. Karim Ben M’Barek. The team is organized into two complementary research groups.

The first group research, led by Prof. Monville, focuses on engineering the outer blood-retinal barrier to model choroidal dysfunction and age-related macular degeneration (AMD). These models are also explored for their therapeutic potential through cell-based approaches evaluated in rodent models of AMD (laser induced lesions of the retina). The second group research, led by Dr. Ben M’Barek, develops tissue-engineered retinal constructs of the neural retina, with a particular focus on photoreceptors. The objective is to develop cell therapies capable of replacing degenerated photoreceptors in advanced stages of AMD and RP. In parallel, this group investigates the mechanisms underlying visual impairment in ciliopathies, particularly Alström syndrome, using human retinal organoids as disease models. Both groups are also addressing several translational challenges required to move the product toward larger-scale clinical use (automation, scale-up, cryopreservation and new quality controls).

Keywords: Retinitis Pigmentosa; Alstrom syndrome; human pluripotent stem cells, cell therapy; choroid; retinal organoid; age-related macular degeneration.