Development of a human RPE In vitro model with AMD-like features reveals blue light-induced modulation of the endocannabinoid system

Blue light (BL) is a known risk factor for age-related macular degeneration (AMD), a retinal pathology where damage to the retinal pigment epithelium (RPE) is one of the earliest events. While the endocannabinoid system (ECS) is implicated in various physio-pathological conditions of the retina, its role in BL-injured RPE has not yet been addressed. To fill this gap, we developed an in vitro model of BL-induced human RPE damage showing key features of AMD: cytotoxicity, cell cycle arrest, oxidative stress, inflammation, and cellular senescence. Notably, our model demonstrates modulation of gene and protein expression of specific ECS elements, particularly cannabinoid receptors 1 and 2 (CB 1 and CB 2 ), thus providing unprecedented evidence of ECS dysregulation in RPE cells upon BL exposure. • Blue Light triggers age-related macular degeneration features in ARPE-19 cells. • Blue light induces cell cycle arrest, oxidative stress, inflammation and senescence. • Blue Light induces selective changes in endocannabinoid system of ARPE-19 cells.