{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:58:21Z","timestamp":1788188301632,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"crossref","award":["JPMJPF2201"],"award-info":[{"award-number":["JPMJPF2201"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"crossref"}]},{"award":["JPMJPF2201"],"award-info":[{"award-number":["JPMJPF2201"]}],"id":[{"id":"https:\/\/ror.org\/00097mb19","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K20188"],"award-info":[{"award-number":["25K20188"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"award":["25K20188"],"award-info":[{"award-number":["25K20188"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Glaucoma is the leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) loss and optic nerve degeneration. While elevated intraocular pressure (IOP) remains the primary modifiable risk factor, a certain proportion of patients continue to deteriorate despite adequate IOP control, pointing to IOP-independent mechanisms of neurodegeneration. Oxidative stress\u2014defined as an imbalance between the production of reactive oxygen species and the capacity of endogenous antioxidant defenses\u2014has emerged as a central, multi-tiered contributor to glaucoma pathogenesis. In the anterior segment, chronic oxidative damage to the trabecular meshwork impairs aqueous humor outflow and drives IOP elevation. In addition, oxidative stress may impair ocular biomechanical integrity, including corneal hysteresis and lamina cribrosa, resulting in heightened susceptibility to IOP fluctuations. In the posterior segment, oxidative stress directly contributes to mitochondrial damage and vascular endothelial injury, leading to RGC apoptosis. The nuclear factor erythroid 2-related factor 2 (Nrf2)\/Kelch-like ECH-associated protein 1 (Keap1) pathway coordinates the principal endogenous antioxidant response, while nicotinamide adenine dinucleotide (NAD+) depletion links redox imbalance to metabolic vulnerability of RGCs. This narrative review synthesizes evidence published up to March 2026 on the molecular mechanisms of oxidative stress in glaucoma, the role of biomarkers in aqueous humor and systemic circulation, and the translational landscape of antioxidant-based neuroprotection\u2014including nicotinamide, coenzyme Q10, alpha-lipoic acid, and Nrf2-activating compounds. We highlight gaps between preclinical promise and clinical evidence, and outline priorities for future randomized controlled trials.<\/jats:p>","DOI":"10.3390\/antiox15060751","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T08:22:56Z","timestamp":1781684576000},"page":"751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oxidative Stress in Glaucoma: From Pathogenic Mechanisms to Emerging Antioxidant Therapies"],"prefix":"10.3390","volume":"15","author":[{"given":"Akiko","family":"Hanyuda","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine, Shinjuku 160-8582, Japan"},{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"},{"name":"Division of Ophthalmic Precision Medicine Development, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2684-0684","authenticated-orcid":false,"given":"Naoki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0720-1265","authenticated-orcid":false,"given":"Masataka","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0176-5545","authenticated-orcid":false,"given":"Kota","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Himori","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"},{"name":"Department of Aging Vision Healthcare, Tohoku University Graduate School of Biomedical Engineering, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Nakazawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"},{"name":"Division of Ophthalmic Precision Medicine Development, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"},{"name":"Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"},{"name":"Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/S0140-6736(10)61423-7","article-title":"Glaucoma","volume":"377","author":"Quigley","year":"2011","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Collaborative Normal-Tension Glaucoma Study Group (1998). 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