Retinal neurodegeneration as accelerated ocular aging: a review of nutritional and metabolic supplements

Retinal neurodegeneration is a major cause of irreversible vision loss and a shared feature of age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma (GL). Increasing evidence suggests that these conditions share important pathways with retinal aging, including mitochondrial dysfunction, metabolic insufficiency, redox imbalance, chronic low-grade inflammation, and progressive neuronal vulnerability. While antioxidant and micronutrient supplementation, most notably the Age-Related Eye Disease Study (AREDS) formulations, has demonstrated benefit in selected AMD populations, emerging metabolic and nutraceutical strategies targeting aging-related pathways are of unproven benefit. In this review, following a brief overview of the current landscape of investigated supplements, we synthesize preclinical and clinical evidence for a group of metabolic supplements, including nicotinamide adenine dinucleotide (NAD ⁺ ) boosters, citicoline, pyruvate, and omega-3 fatty acids, that directly modulate mitochondrial bioenergetics, cellular redox state, membrane integrity, and neuroinflammatory signaling—pathways that are recognized hallmarks of biological aging and are particularly relevant to aging-related processes implicated in retinal neurodegeneration. Using a structured literature and clinical trial search, we summarize mechanistic insights and translational findings across AMD, DR, and glaucoma, emphasizing convergence on core pathways linking retinal neurodegeneration and ocular aging. Overall, current evidence supports biological plausibility and early functional or biomarker signals for these agents, particularly in glaucoma and diabetic retinal disease, although long-term efficacy remains unproven. Framing retinal disease at the intersection of neurodegeneration and aging biology, this review highlights metabolic supplementation as a promising but evolving strategy for preserving retinal function.