Immunological drivers of oxidative stress in glaucoma: implications for antioxidant therapy

Glaucoma is a progressive neurodegenerative disorder characterized by RGC loss and irreversible visual impairment, representing the second leading cause of global blindness. Immune-inflammatory responses and oxidative stress are core pathological drivers of glaucomatous optic nerve degeneration, forming a vicious cycle via the TLR4/NF-κB/NLRP3 inflammasome axis, complement overactivation, and dysregulation of the endogenous antioxidant system. These processes trigger sustained neuroinflammation, mitochondrial dysfunction, and RGC apoptosis. Antioxidant therapies targeting the immune-oxidative stress axis have emerged as promising neuroprotective strategies, including classic antioxidants, Nrf2 activators (e.g., NOB), nanocarrier-mediated targeted delivery systems, and PBM. This mini-review summarizes key molecular mechanisms linking immune activation and oxidative damage in glaucoma, reviews recent advances in the development of antioxidant therapeutics, and discusses current challenges and future directions for clinical translation.