Long-term daily light exposure boosts human retinal organoid differentiation

Induced pluripotent stem cell-derived retinal organoids (ROs) have become promising personalized models to study inherited retinal diseases (IRDs) and develop new therapies. Although ROs mimic key retinal features and show some light responsiveness, their differentiation and maturation remain limited and lengthy. We hypothesize that standard dark culture conditions limit the expression of genes and proteins related to retinal function, delaying differentiation, and hindering disease modeling. Here, we investigate whether daily light exposure promotes photoreceptor maturation by exposing ROs to six hours of daily light starting from day 70 in vitro. Light conditioning accelerates differentiation of late-born cell types, especially rod photoreceptors, without signs of increased stress or cell death. Our findings suggest that daily light exposure enhances RO differentiation, opening avenues to investigate molecular and cellular phenotypes in IRDs and accelerate therapy development in more relevant functional models.