Photobiology in ophthalmology: from evolutionary adaptation to translational therapeutics

Life has evolved under continuous exposure to solar light, and the emergence of the eye during the Cambrian period is thought to have accelerated biological diversification. Beyond vision, light acts as a biological regulator of metabolism and tissue organization. To elucidate ocular disease mechanisms and develop new therapies, we have investigated how light is sensed by the eye and coupled to physiological and pathological responses. This review reexamines the eye as a photoreceptive organ and summarizes recent advances showing how light input governs retinal metabolism, refractive development, and visual restoration. First, we describe how retinal light reception is linked to oxygen-dependent metabolic control. As one of the most oxygen-demanding tissues, the retina relies on hypoxia-inducible factor (HIF) signaling to coordinate angiogenesis, mitochondrial metabolism, fibrosis, and neuronal survival. Beyond pathological neovascularization, disrupted light-metabolic coupling contributes to neurodegeneration and subretinal scarring. Screening of natural compounds identified HIF regulators with therapeutic efficacy, and optical approaches were developed to detect hypoxia-induced intraocular cytokines noninvasively. Second, we show that environmental light regulates ocular growth in ways beyond image formation. Violet light activates nonvisual photoreception via OPN5-expressing retinal ganglion cells, engaging an OPN5-EGR1 pathway that preserves choroidal thickness and suppresses axial elongation through coordinated retina-brain-choroid-sclera interactions. Third, we demonstrate that light itself becomes therapeutic through optogenetic visual restoration. Chimeric rhodopsins confer high-sensitivity light responsiveness to surviving inner retinal neurons and have recently entered first-in-human clinical evaluation for advanced retinitis pigmentosa. These findings establish photobiology as a unifying framework for translational ophthalmology.