The Retina as a Bridge to the Brain: Shared Neurodegenerative Mechanisms and Therapeutic Perspectives

The eye is a highly specialized structure that allows humans to know, understand and recognize the world around them through vision. The retina represents a specialized anatomical and functional extension of the central nervous system. Increasing evidence suggests that multiple retinal disorders share common molecular and cellular pathways with neurodegenerative diseases of the brain. This review explores the concept of the retina as a biological bridge to the brain, emphasizing the structural, embryological and physiological continuity between these systems. We analyze key mechanisms involved in both retinal and brain degeneration, including glutamate dysregulation and excitotoxicity, optic neuritis and demyelination, vascular dysfunction and glymphatic system impairment. These mechanisms contribute to neuronal damage through mitochondrial dysfunction, oxidative stress, disruption of blood-tissue barriers and persistent neuroinflammation. Retinal ganglion cells, due to their high metabolic demand and mitochondrial vulnerability, emerge as particularly susceptible targets of these pathological processes. This review also highlights parallels between retinal and neurodegenerative disorders, including neuronal death driven by glutamate excitotoxiciy, optic neuritis and multiple sclerosis and the mechanistic links between glaucoma and Alzheimer’s disease. Finally, emerging therapeutic strategies are discussed, with particular focus on stem cell and exosome therapies. Through immunomodulatory, neuromodulatory and bioenergetic mechanisms these approaches may offer multi-target strategies capable of addressing complex neurodegenerative disorders affecting both the retina and the brain.