{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:41:54Z","timestamp":1778643714530,"version":"3.51.4"},"reference-count":67,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T00:00:00Z","timestamp":1774051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1105500"],"award-info":[{"award-number":["2022YFA1105500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Early diagnosis of glaucoma remains challenging due to its asymptomatic onset and multifactorial pathological mechanisms. Growing evidence indicates that metabolic disorders and systemic molecular alterations play significant roles in glaucoma pathogenesis. However, reliable biomarkers and corresponding specific mechanisms remain unclear. In this study, we employed a multi-omics approach that encompassed metabolomics, transcriptomics, and Mendelian randomization to investigate the association between glaucoma and 35 types of blood and urine biomarkers. Metabolic pathway analysis was conducted using pathway enrichment analysis of differentially expressed genes based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Our study indicated that glaucoma contributed to elevated calcium concentration (OR = 1.044, 95% CI: 1.002\u20131.088, p = 0.039) in blood and urine, mediated by cell membrane calcium channels and calcium release from intracellular storage. Conversely, glucose was found to contribute to high glaucoma risk (OR = 1.324, 95% CI: 1.143\u20131.533, p = 0.0002), mediated by increased aqueous humor production, elevated intraocular pressure, endoplasmic reticulum stress, and oxidative stress. Validation experiments showed that calcium levels in blood, urine, and retina were elevated in the glaucoma group, and elevated glucose levels significantly reduced the 661W cell viability and induced apoptosis. This study offers new insights into the specific mechanisms linking blood and urine biomarkers to glaucoma, contributing to its prevention and screening.<\/jats:p>","DOI":"10.3390\/ijms27062848","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T09:48:42Z","timestamp":1774259322000},"page":"2848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unveiling Systemic Biomarkers and Metabolic Mechanisms in Glaucoma Progression from Multi-Omics Insights"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0439-656X","authenticated-orcid":false,"given":"Shengshu","family":"Sun","sequence":"first","affiliation":[{"name":"Senior Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Xu","sequence":"additional","affiliation":[{"name":"Senior Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge","family":"Bai","sequence":"additional","affiliation":[{"name":"Senior Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youhan","family":"Ao","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin 300071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An","family":"Wang","sequence":"additional","affiliation":[{"name":"Senior Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaying","family":"Sun","sequence":"additional","affiliation":[{"name":"Senior Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1078-2515","authenticated-orcid":false,"given":"Yifei","family":"Huang","sequence":"additional","affiliation":[{"name":"Senior Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1718-0453","authenticated-orcid":false,"given":"Liqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Senior Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Medical School of Chinese People\u2019s Liberation Army, Beijing 100853, China"},{"name":"School of Medicine, Nankai University, Tianjin 300071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101291","DOI":"10.1016\/j.preteyeres.2024.101291","article-title":"The AI revolution in glaucoma: Bridging challenges with opportunities","volume":"103","author":"Li","year":"2024","journal-title":"Prog. 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