Environmental Exposures and Oxidative Stress in Retinal and Optic Nerve Diseases: Mechanisms, Consequences, and Therapeutic Opportunities

Oxidative stress is a key contributing and convergent pathogenic mechanism linked to retinal and optic nerve diseases including age-related macular degeneration, diabetic retinopathy, and glaucoma. The retina is highly susceptible to redox imbalance due to intense mitochondrial activity, oxygen consumption, and light exposure. While endogenous drivers are well recognized, the contribution of environmental exposure to retinal oxidative injury remains incompletely defined. This review uniquely integrates emerging environmental contaminants with canonical oxidative stress pathways. We examine how cigarette smoke, ultraviolet radiation, heavy metals, microplastics, and per- and polyfluoroalkyl substances (PFASs) promote oxidative injury through mitochondrial dysfunction, inflammatory signaling, impaired antioxidant responses, and ferroptotic pathways. We also highlight therapeutic strategies targeting oxidative pathways and emphasize the importance of exposure-informed retinal and optic nerve disease research.