{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:02:55Z","timestamp":1789448575957,"version":"build-2803163510"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To explore the plasma metabolite profiles of patients with early primary angle-closure glaucoma (PACG) and investigate their relevance to ocular characteristics and retinal-associated parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma samples were obtained from 30 early PACG patients and 30 healthy controls for untargeted and targeted metabolomics analysis. Additionally, relevant clinical data such as ocular characteristics and retinal-associated parameters were collected. Correlations between clinical data and differential metabolites were further analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 439 differential metabolites were identified through untargeted metabolomics analysis, with amino acids being the most abundant category among the differential metabolites. Amino acid-targeted metabolomics revealed that L-alanine, L-lysine, citrulline, L-tyrosine, and glycylglycine were significantly elevated in early PACG (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05). In addition, intraocular pressure (IOP) was significantly higher (20.9\u2009\u00b1\u20092.5 vs. 14.2\u2009\u00b1\u20092.4\u2005mmHg,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001), axial length (AL) was shorter (22.8\u2009\u00b1\u20090.1 vs. 23.2\u2009\u00b1\u20090.2\u2005mm,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001), and lens thickness (LT) was greater (4.8\u2009\u00b1\u20090.2 vs. 4.3\u2009\u00b1\u20090.2\u2005mm,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001) in early PACG patients than in healthy controls. Reduced retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, and superficial vascular complex vessel density in the peripapillary and macular regions were observed in early PACG patients compared with healthy controls (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05). We further identified five amino acids that showed a positive correlation with IOP and LT, and a negative correlation with AL, as well as with the thickness of the RNFL and GCC in the central 3\u20136\u2005mm annular region (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The plasma of early PACG patients showed distinctive metabolic profiles, which provided new insights into the pathogenesis of the early phase of PACG patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1928552","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:26:55Z","timestamp":1789446415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma amino acid metabolic alterations and their associations with ocular parameters in early primary angle-closure glaucoma"],"prefix":"10.3389","volume":"13","author":[{"given":"Hui","family":"Liu","sequence":"first","affiliation":[{"name":"Hebei Medical University Clinical Medicine Postdoctoral Research Station (The Second Hospital)","place":["Shijiazhuang, Hebei, China"]},{"name":"Department of Ophthalmology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1016\/S0140-6736(23)01289-8","article-title":"Glaucoma: now and beyond","volume":"402","author":"Jayaram","year":"2023","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e61","DOI":"10.1097\/IJG.0000000000001745","article-title":"Optical coherence tomography angiography and visual field progression in primary angle closure glaucoma","volume":"30","author":"Rao","year":"2021","journal-title":"J Glaucoma"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1016\/j.ophtha.2014.01.021","article-title":"Optical coherence tomography angiography of optic disc perfusion in glaucoma","volume":"121","author":"Jia","year":"2014","journal-title":"Ophthalmology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1001\/jamaophthalmol.2015.2225","article-title":"Optical coherence tomography angiography of the peripapillary retina in glaucoma","volume":"133","author":"Liu","year":"2015","journal-title":"JAMA Ophthalmol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.ajo.2016.08.030","article-title":"Regional comparisons of optical coherence tomography angiography vessel density in primary open-angle glaucoma","volume":"171","author":"Rao","year":"2016","journal-title":"Am J Ophthalmol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1093\/hmg\/ddy053","article-title":"Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma","volume":"27","author":"Shiga","year":"2018","journal-title":"Hum Mol Genet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"103368","DOI":"10.1016\/j.redox.2024.103368","article-title":"Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomics","volume":"77","author":"Rejas-Gonz\u00e1lez","year":"2024","journal-title":"Redox Biol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1016\/j.neuron.2022.06.022","article-title":"Single-cell transcriptome analysis of regenerating RGCs reveals potent glaucoma neural repair genes","volume":"110","author":"Li","year":"2022","journal-title":"Neuron"},{"key":"B9","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jpsychires.2019.09.009","article-title":"Peripheral biomarkers allow differential diagnosis between schizophrenia and bipolar disorder","volume":"119","author":"Tasic","year":"2019","journal-title":"J Psychiatr Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"108070","DOI":"10.1016\/j.exer.2020.108070","article-title":"Plasma metabolomics study of Vogt-Koyanagi-Harada disease identifies potential diagnostic biomarkers","volume":"196","author":"Chen","year":"2020","journal-title":"Exp Eye Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1007\/s13361-016-1469-y","article-title":"Untargeted metabolomics strategies-challenges and emerging directions","volume":"27","author":"Schrimpe-Rutledge","year":"2016","journal-title":"J Am Soc Mass Spectrom"},{"key":"B12","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41433-019-0634-5","article-title":"Has the EAGLE landed for the use of clear lens extraction in angle-closure glaucoma? And how should primary angle-closure suspects be treated?","volume":"34","author":"Tanner","year":"2020","journal-title":"Eye"},{"key":"B13","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.jcjo.2020.12.010","article-title":"Clinical characteristics, rates of blindness, and geographic features of PACD in China","volume":"56","author":"Zhang","year":"2021","journal-title":"Can J Ophthalmol"},{"key":"B14","volume-title":"Clinical Decisions in Glaucoma","author":"Chang","year":"2016"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1016\/S0161-6420(00)00284-0","article-title":"Mapping the visual field to the optic disc in normal tension glaucoma eyes","volume":"107","author":"Garway-Heath","year":"2000","journal-title":"Ophthalmology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1021\/ac051312t","article-title":"Solvent-dependent metabolite distribution, clustering, and protein extraction for serum profiling with mass spectrometry","volume":"78","author":"Want","year":"2006","journal-title":"Anal Chem"},{"key":"B17","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.aca.2013.01.015","article-title":"UPLC-ESI-QTOF\/MS and multivariate data analysis for blood plasma and serum metabolomics: effect of experimental artefacts and anticoagulant","volume":"768","author":"Barri","year":"2013","journal-title":"Anal Chim Acta"},{"key":"B18","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1186\/s12872-024-04306-y","article-title":"Plasma metabolomic characteristics of atrial fibrillation patients with spontaneous echo contrast","volume":"24","author":"Shi","year":"2024","journal-title":"BMC Cardiovasc Disord"},{"key":"B19","doi-asserted-by":"publisher","first-page":"107921","DOI":"10.1016\/j.exer.2020.107921","article-title":"Gut microbiota compositional profile and serum metabolic phenotype in patients with primary open-angle glaucoma","volume":"191","author":"Gong","year":"2020","journal-title":"Exp Eye Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.3963","article-title":"Long-chain unsaturated fatty acids as possible important metabolites for primary angle-closure glaucoma based on targeted metabolomic analysis","volume":"31","author":"Rong","year":"2017","journal-title":"Biomed Chromatogr"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5020","DOI":"10.1167\/iovs.15-16702","article-title":"Metabolome-wide association study of primary open angle glaucoma","volume":"56","author":"Burgess","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B22","doi-asserted-by":"publisher","first-page":"109366","DOI":"10.1016\/j.exer.2022.109366","article-title":"Relationship between plasma amino acid and carnitine levels and primary angle-closure glaucoma based on mass spectrometry metabolomics","volume":"227","author":"Zhang","year":"2023","journal-title":"Exp Eye Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"110418","DOI":"10.1016\/j.exer.2025.110418","article-title":"Oleic acid association with primary angle-closure glaucoma: a finding using metabolomics","volume":"256","author":"Qi","year":"2025","journal-title":"Exp Eye Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"307","DOI":"10.3390\/biom14030307","article-title":"Untargeted and oxylipin-targeted metabolomics study on the plasma samples of primary open-angle glaucoma patients","volume":"14","author":"Xu","year":"2024","journal-title":"Biomolecules"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e002103","DOI":"10.1136\/bmjophth-2024-002103","article-title":"Identifying potential key metabolic pathways and biomarkers in glaucoma: a systematic review and meta-analysis","volume":"10","author":"Golpour","year":"2025","journal-title":"BMJ Open Ophthalmol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1021\/acs.jproteome.8b00915","article-title":"Metabolomic profiling of aqueous humor in glaucoma points to taurine and spermine deficiency: findings from the eye-D study","volume":"18","author":"Buisset","year":"2019","journal-title":"J Proteome Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1126\/science.aal0092","article-title":"Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice","volume":"355","author":"Williams","year":"2017","journal-title":"Science"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1403844","DOI":"10.3389\/fmolb.2024.1403844","article-title":"Metabolomics studies in common multifactorial eye disorders: a review of biomarker discovery for age-related macular degeneration, glaucoma, diabetic retinopathy and myopia","volume":"11","author":"Belete","year":"2024","journal-title":"Front Mol Biosci"},{"key":"B29","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.exer.2008.01.013","article-title":"Extracellular matrix in the trabecular meshwork","volume":"86","author":"Acott","year":"2008","journal-title":"Exp Eye Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/S1350-9462(02)00008-3","article-title":"The impact of ocular blood flow in glaucoma","volume":"21","author":"Flammer","year":"2002","journal-title":"Prog Retin Eye Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"4355","DOI":"10.1167\/iovs.18-24938","article-title":"A metabolomics profiling of glaucoma points to mitochondrial dysfunction, senescence, and polyamines deficiency","volume":"59","author":"Leruez","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3390\/metabo10020049","article-title":"A data mining metabolomics exploration of glaucoma","volume":"10","author":"Kouassi Nzoughet","year":"2020","journal-title":"Metabolites"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1167\/iovs.17-23055","article-title":"A plasma metabolomic signature of the exfoliation syndrome involves amino acids, acylcarnitines, and polyamines","volume":"59","author":"Leruez","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B34","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1097\/IJG.0000000000000900","article-title":"Reduced retinal vessel density in primary angle closure glaucoma: a quantitative study using optical coherence tomography angiography","volume":"27","author":"Zhu","year":"2018","journal-title":"J Glaucoma"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1136\/bjophthalmol-2016-309377","article-title":"Diagnostic ability of peripapillary vessel density measurements of optical coherence tomography angiography in primary open-angle and angle-closure glaucoma","volume":"101","author":"Rao","year":"2017","journal-title":"Br J Ophthalmol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1928552\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:26:56Z","timestamp":1789446416000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1928552\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":35,"alternative-id":["10.3389\/fmed.2026.1928552"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1928552","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"1928552"}}