Photobiomodulation for Photoreceptor Rescue in Retinal Disease: Mitochondrial, Redox, Vascular, and Translational Perspectives-A Narrative Review.

Photoreceptors work in a biologically demanding compartment of the eye. They consume large amounts of energy, receive continuous light and oxygen, and renew outer-segment membranes enriched in polyunsaturated lipids. These conditions are necessary for vision, but they also make the outer retina poorly tolerant to persistent mitochondrial dysfunction and oxidative stress. Photobiomodulation (PBM), mainly based on red and near-infrared light, has been investigated as a way to support retinal cells that are functionally impaired but not yet irreversibly lost. The field has also acquired new clinical relevance after the 2024 De Novo marketing authorization by the United States Food and Drug Administration (FDA) of the Valeda Light Delivery System for dry age-related macular degeneration (AMD). This narrative review examines the mitochondrial, redox, inflammatory, and neurovascular mechanisms proposed for PBM, and discusses preclinical and clinical evidence across nonexudative AMD, inherited retinal degeneration, diabetic retinal disease, and light-induced damage. Current findings are encouraging, but devices, doses, schedules, endpoints, and sponsorship patterns differ substantially among studies. PBM therefore deserves further investigation, especially in early or intermediate disease, but its clinical use should remain linked to tested protocols, rigorous safety monitoring, and biomarkers of residual retinal functional reserve.