{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:03:12Z","timestamp":1785402192511,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82500499"],"award-info":[{"award-number":["82500499"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82500499"],"award-info":[{"award-number":["82500499"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness driven by elevated intraocular pressure from compromised aqueous outflow. While genome-wide association studies have identified numerous risk loci, specific candidate proteins and their cellular mechanisms remain elusive. We employed a multi-omics framework integrating UK Biobank plasma proteomics (N = 53,022) and large-scale POAG GWAS summary statistics. We performed a Proteome-Wide Association Study, Mendelian Randomization, and Bayesian colocalization to infer causality. Identified candidates were mapped to human and mouse ocular scRNA-seq atlases to characterize cell-type specificity, followed by druggability assessments. We prioritized five putative causal proteins, with SEL1L and TFPI demonstrating the strongest evidence. Cross-species scRNA-seq revealed that SEL1L and SERPINF1 are robustly expressed in the trabecular meshwork (TM), particularly the juxtacanalicular tissue, implicating them in outflow resistance. Conversely, TFPI and SLC9A3R2 localize to Schlemm\u2019s canal endothelium, suggesting a role in modulating barrier function. Pathway analyses highlighted endoplasmic reticulum protein processing and coagulation cascades. This study maps putative causal POAG proteins to conventional outflow pathway cells, highlighting SEL1L as a novel target for TM homeostasis and TFPI for drug repurposing, thereby providing data-driven hypotheses to facilitate precision glaucoma therapeutics.<\/jats:p>","DOI":"10.3390\/ijms27114684","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T16:06:08Z","timestamp":1779465968000},"page":"4684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Multi-Omics Analysis Prioritizes Candidate Therapeutic Targets for Primary Open-Angle Glaucoma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4946-7897","authenticated-orcid":false,"given":"Hao","family":"Kan","sequence":"first","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi 214126, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214126, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wen","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi 214126, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi 214126, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi 214126, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiqin","family":"Mao","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi 214126, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Geng","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi 214126, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yu","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi 214126, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4997-1679","authenticated-orcid":false,"given":"Lei","family":"Feng","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi 214126, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/S0140-6736(04)16257-0","article-title":"Primary open-angle glaucoma","volume":"363","author":"Weinreb","year":"2004","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","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":"ref_3","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1001\/jama.2019.16161","article-title":"Association of Genetic Variants with Primary Open-Angle Glaucoma Among Individuals with African Ancestry","volume":"322","author":"Hauser","year":"2019","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/s41588-023-01428-5","article-title":"Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci","volume":"55","author":"Han","year":"2023","journal-title":"Nat. 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