{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:53:13Z","timestamp":1776837193162,"version":"3.51.2"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T00:00:00Z","timestamp":1562025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Miller Retina Research Fund (Mass. Eye and Ear), Champalimaud Vision Award (JWM), unrestricted departmental Grant from Research to Prevent Blindness, Commonwealth Unrestricted Grant for Eye Research.","award":["000000"],"award-info":[{"award-number":["000000"]}]},{"name":"Portuguese Foundation for Science and Technology\/ Harvard Medical School Portugal Program (HMSP-ICJ\/006\/2013 : (HMSP-ICJ\/006\/2013","award":["(HMSP-ICJ\/006\/2013"],"award-info":[{"award-number":["(HMSP-ICJ\/006\/2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness worldwide, remains only partially understood. This has led to the current lack of accessible and reliable biofluid biomarkers for diagnosis and prognosis, and absence of treatments for dry AMD. This study aimed to assess the plasma metabolomic profiles of AMD and its severity stages with the ultimate goal of contributing to addressing these needs. We recruited two cohorts: Boston, United States (n = 196) and Coimbra, Portugal (n = 295). Fasting blood samples were analyzed using ultra-high performance liquid chromatography mass spectrometry. For each cohort, we compared plasma metabolites of AMD patients versus controls (logistic regression), and across disease stages (permutation-based cumulative logistic regression considering both eyes). Meta-analyses were then used to combine results from the two cohorts. Our results revealed that 28 metabolites differed significantly between AMD patients versus controls (false discovery rate (FDR) q-value: 4.1 \u00d7 10\u22122\u20131.8 \u00d7 10\u22125), and 67 across disease stages (FDR q-value: 4.5 \u00d7 10\u22122\u20131.7 \u00d7 10\u22124). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (p-value \u2264 0.04). In conclusion, our findings support that AMD patients present distinct plasma metabolomic profiles, which vary with disease severity. This work contributes to the understanding of AMD pathophysiology, and can be the basis of future biomarkers and precision medicine for this blinding condition.<\/jats:p>","DOI":"10.3390\/metabo9070127","type":"journal-article","created":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T12:11:17Z","timestamp":1562069477000},"page":"127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts"],"prefix":"10.3390","volume":"9","author":[{"given":"In\u00eas","family":"La\u00edns","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Faculty of Medicine, University of Coimbra, 3000 Coimbra, Portugal"},{"name":"Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000 Coimbra, Portugal"},{"name":"Association for Innovation and Biomedical Research on Light and Image, 3000 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5766-6247","authenticated-orcid":false,"given":"Wonil","family":"Chung","sequence":"additional","affiliation":[{"name":"Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}]},{"given":"Rachel S.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Systems Genetics and Genomics Unit, Channing Division of Network Medicine Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}]},{"given":"Jo\u00e3o","family":"Gil","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Coimbra, 3000 Coimbra, Portugal"}]},{"given":"Marco","family":"Marques","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Coimbra, 3000 Coimbra, Portugal"}]},{"given":"Patr\u00edcia","family":"Barreto","sequence":"additional","affiliation":[{"name":"Association for Innovation and Biomedical Research on Light and Image, 3000 Coimbra, Portugal"}]},{"given":"Joaquim N.","family":"Murta","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Coimbra, 3000 Coimbra, Portugal"},{"name":"Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000 Coimbra, Portugal"},{"name":"Association for Innovation and Biomedical Research on Light and Image, 3000 Coimbra, Portugal"}]},{"given":"Ivana K.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA"}]},{"given":"Demetrios G.","family":"Vavvas","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA"}]},{"given":"John B.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8676-0833","authenticated-orcid":false,"given":"Rufino","family":"Silva","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Coimbra, 3000 Coimbra, Portugal"},{"name":"Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000 Coimbra, Portugal"},{"name":"Association for Innovation and Biomedical Research on Light and Image, 3000 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6236-4705","authenticated-orcid":false,"given":"Jessica","family":"Lasky-Su","sequence":"additional","affiliation":[{"name":"Systems Genetics and Genomics Unit, Channing Division of Network Medicine Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}]},{"given":"Liming","family":"Liang","sequence":"additional","affiliation":[{"name":"Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}]},{"given":"Joan W.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA"}]},{"given":"Deeba","family":"Husain","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. 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