Long-term daily light exposure boosts photoreceptor maturation in retinal organoids

Induced pluripotent stem cell-derived retinal organoids (ROs) have become promising personalized models to study inherited retinal diseases (IRDs) and develop new innovative 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 complicating disease modeling. Therefore, we investigated whether daily light exposure could promote photoreceptor maturation. ROs were exposed to six hours of daily light starting from day 70 in vitro . Light conditioning led to enhanced photoreceptor maturation, specifically an increase in rod photoreceptors, a late-born cell type, without signs of increased stress or cell death. Our findings suggest that daily light exposure enhances RO differentiation, opening new avenues to investigate molecular and cellular phenotypes in IRDs and accelerate therapy development in more relevant functional models.