Association between systemic oxidative stress and visual field damage in open-angle glaucoma

Glaucoma is a leading cause of irreversible blindness worldwide1 including in Japan2. The death of retinal ganglion cells (RGCs) and RGC axon loss causes glaucomatous optic neuropathy, in which elevated intraocular pressure (IOP) is the primary risk factor3. The IOP in patients with primary open-angle glaucoma (POAG) increases because of reduced aqueous humor outflow at the trabecular meshwork (TM)4. Treatment using hydrogen peroxide affects the cytoskeletal structure and cell-matrix interactions in TM cells5; depletion of glutathione and hydrogen peroxide treatment decrease the TM outflow facility6. Oxidative stress results from formation of multiple reactive oxygen species including superoxide, hydrogen peroxide, and hydroxyl radicals that can help in the formation and propagation of free radicals. The net oxidative burden between the prooxidant and antioxidant systems is oxidative stress, which damages cellular and tissue macromolecules, resulting in cellular and tissue dysfunction and death. Various oxidative stresses have been reported to induce RGC death in experimental studies7,8, and free-radical scavengers prevent glaucomatous tissue injury, specifically, glutamate- and IOP-induced RGC death9,10 and tumor necrosis factor α-induced axonal injury11. Evidence suggests that oxidative stress is involved in IOP elevations and RGC loss in POAG and POAG without marked IOP elevation such as that in normal tension glaucoma (NTG). We reported significantly lower systemic antioxidant capacity levels in patients with OAG including POAG and glaucoma secondary to exfoliation syndrome (EX) compared with controls12. Although some studies found a correlation between glaucoma severity (i.e., IOP or visual field damage) and ocular13,14 or systemic15,16 levels of oxidative stress in humans, the role of systemic oxidative stress in the pathogenesis of glaucoma is largely unknown. We investigated a possible correlation between visual field damage and systemic levels of prooxidants and antioxidants in OAG (i.e., POAG and NTG).