Nrf2/HO-1 signaling in retinal neurodegenerative diseases: redox homeostasis, cytoprotection, and therapeutic perspectives.

Retinal neurodegenerative diseases (RNDs) represent a major group of disorders leading to irreversible visual impairment. Persistent oxidative stress, mitochondrial dysfunction, inflammatory responses, lipid peroxidation, and disruption of neurovascular unit homeostasis are closely implicated in retinal neuronal and vascular injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream effector heme oxygenase-1 (HO-1) constitute a key regulatory axis in cellular antioxidant defense and adaptive stress responses. Current preclinical evidence suggests that Nrf2/HO-1 signaling may participate in retinal cytoprotection, inflammatory regulation, and maintenance of neurovascular homeostasis in RNDs by modulating redox homeostasis and interconnected injury responses. This review critically synthesizes the cytoprotective roles, evidence boundaries, translational challenges, and future directions of Nrf2/HO-1 signaling in RNDs, organized around retinal cell types, redox homeostasis-related injury mechanisms, disease-specific evidence, and intervention strategies. Further translation will require stronger causal validation, improved ocular delivery, and better cell type-specific targeting.