From Retina to Vasculature: Oxidative Stress as a Common Mechanistic Link Between Age-Related Macular Degeneration and Cardiovascular Disease

Abstract

Increasing epidemiological and experimental evidence suggests that age-related macular degeneration (AMD) and cardiovascular disease (CVD) share multiple pathogenic mechanisms. Among these, oxidative stress has emerged as one of the most plausible links connecting retinal degeneration and cardiovascular pathology. Excessive production of reactive oxygen and nitrogen species, combined with declining antioxidant defenses, contributes to lipid peroxidation, mitochondrial dysfunction, chronic inflammation, complement activation, cellular senescence, and impaired cellular stress responses in both the retina and the vascular system. Notably, drusen (AMD) and atherosclerotic plaques (CVD) share several molecular constituents. Therefore, AMD and CVD may represent tissue-specific manifestations of broader age-related disturbances in redox homeostasis and inflammatory regulation. Nevertheless, the coexistence of AMD and CVD is incomplete, suggesting that genetic susceptibility, tissue-specific responses to oxidative stress, biological aging, and mechanisms of cellular resilience influence disease expression. In this review, we summarize current evidence linking AMD and CVD, examine oxidative stress-driven molecular pathways common to both disorders, discuss emerging biomarkers and therapeutic targets, and highlight important unresolved questions regarding disease heterogeneity and causal relationships. A better understanding of the shared mechanisms underlying AMD and CVD may facilitate the development of integrated preventive strategies, improved risk stratification, and more personalized therapeutic approaches for age-related diseases.