The Eye as a Window to Neurodegeneration: Oxidative Stress, Optic Nerve Vulnerability, and Retinal Biomarkers. A Scoping Review

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Neurodegenerative diseases represent a major and growing global health burden characterized by progressive neuronal dysfunction, axonal degeneration, and irreversible neural tissue loss. Increasing evidence identifies oxidative stress as a central pathogenic mechanism in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and several optic neuropathies. Interest has increasingly focused on the brain-retina axis, as the retina and optic nerve share structural, metabolic, and molecular features with the central nervous system and may provide accessible insights into neurodegeneration.This scoping review mapped current evidence on oxidative stress in neurodegeneration, emphasizing cranial nerve involvement, optic nerve vulnerability, retinal ganglion cell degeneration, visual dysfunction, oxidative biomarkers, and emerging therapeutic strategies. The review followed established methodological frameworks and PRISMA-ScR recommendations.The literature shows that oxidative stress interacts with mitochondrial dysfunction, neuroinflammation, impaired mitophagy, ferroptosis, and altered bioenergetics, contributing to neuronal injury in cerebral and retinal disorders. Retinal ganglion cells appear particularly vulnerable because of their high metabolic demands and reliance on oxidative phosphorylation. Glaucoma and other optic neuropathies share molecular signatures with central neurodegenerative diseases. Retinal imaging and oxidative biomarkers show promise for diagnosis, monitoring, and stratification. Overall, oxidative stress emerges as a convergent mechanism across the brain-retina continuum, supporting biomarker-driven neuroprotection and precision medicine.

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