{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:30:40Z","timestamp":1789475440646,"version":"build-2803163510"},"reference-count":35,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"unspecified","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008738","name":"Jeanssons Stiftelser","doi-asserted-by":"publisher","award":["J2021-0041"],"award-info":[{"award-number":["J2021-0041"]}],"id":[{"id":"10.13039\/100008738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2022-00799"],"award-info":[{"award-number":["2022-00799"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Ophth"],"accepted":{"date-parts":[[2025,2,14]]},"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glaucoma, a leading cause of irreversible blindness worldwide, is characterised by retinal ganglion cell degeneration. Increasing evidence points to metabolic dysfunction, particularly mitochondrial dysfunction, as a contributing factor to glaucomatous neurodegeneration. This systematic review and meta-analysis aimed to identify key metabolic pathways and biomarkers associated with primary open-angle glaucoma (POAG).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic literature search was conducted to identify studies measuring metabolites in plasma and aqueous humour from patients with POAG using metabolomics techniques. Enrichment analyses for significantly increased metabolites were conducted using MetaboAnalyst. Meta-analyses were performed using random-effects models to calculate effect sizes for metabolites reported in at least three studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>17 studies involving patients with POAG were included. Pathway analysis revealed significant enrichment of the arginine and proline metabolism pathway in both aqueous humour and plasma. Additionally, the phenylalanine metabolism pathway was enriched in plasma. These pathways are associated with oxidative stress and neurodegeneration, both of which are key factors in POAG pathology. Meta-analysis identified several significantly elevated metabolites, including lysine, glutamine, alanine, histidine, carnitine and creatinine in aqueous humour, as well as methionine in plasma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study underscores the central role of metabolic dysfunction in POAG, highlighting specific metabolites and pathways that could serve as biomarkers for early diagnosis and therapeutic intervention. Future research should prioritise longitudinal studies and untargeted metabolomic profiling to further deepen our understanding of metabolic changes and their contributions to glaucoma progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD42024512098.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjophth-2024-002103","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T23:10:17Z","timestamp":1741907417000},"page":"e002103","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Identifying potential key metabolic pathways and biomarkers in glaucoma: a systematic review and meta-analysis"],"prefix":"10.1136","volume":"10","author":[{"given":"Navid","family":"Golpour","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rune L","family":"Brautaset","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Hui","sequence":"additional","affiliation":[{"name":"Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas E","family":"Svensson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6194-8397","authenticated-orcid":false,"given":"Pete A","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8301-7358","authenticated-orcid":false,"given":"James R","family":"Tribble","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"2026010721202901000_10.1.e002103.1","doi-asserted-by":"crossref","first-page":"e1221","DOI":"10.1016\/S2214-109X(17)30393-5","article-title":"Global causes of blindness and distance vision impairment 1990\u20132020: a systematic review and meta-analysis","volume":"5","author":"Flaxman","year":"2017","journal-title":"Lancet Glob Health"},{"key":"2026010721202901000_10.1.e002103.2","unstructured":"Hoste AM . 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