{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:35:33Z","timestamp":1793054133711,"version":"4.5.0"},"reference-count":91,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01EY030218,R01EY032905,RO1EY017006"],"award-info":[{"award-number":["R01EY030218,R01EY032905,RO1EY017006"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT168845,PJT166201"],"award-info":[{"award-number":["PJT168845,PJT166201"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,8]]},"abstract":"<jats:p>\n                    Synthetic prostaglandin analogs, such as latanoprost, are first-line treatments to reduce intraocular pressure (IOP) in the management of glaucoma, treating millions of patients daily. Glaucoma is a leading cause of blindness, characterized by progressive optic neuropathy, with elevated IOP being the sole modifiable risk factor. Despite this importance, the underlying latanoprost mechanism of action is still not well defined, being associated with both acute and long-term activities, and a growing list of ocular side effects. Prostaglandins are eicosanoid lipid mediators. Yet, there has not been a comprehensive assessment of small lipid mediators in glaucomatous eyes. Here, we performed a lipidomic screen of aqueous humor sampled from patients with glaucoma and healthy control eyes. The resulting signature was surprisingly focused on significantly elevated levels of arachidonic acid (AA) and its derivative, the antiinflammatory and cytoprotective mediator, lipoxin A\n                    <jats:sub>4<\/jats:sub>\n                    (LXA\n                    <jats:sub>4<\/jats:sub>\n                    ), in glaucomatous eyes. Subsequent experiments revealed that this response was drug induced, due to latanoprost actions on trabecular meshwork cells, rather than a consequence of elevated IOP. We demonstrate that increased LXA\n                    <jats:sub>4<\/jats:sub>\n                    inhibited proinflammatory cues and promoted TGF-\u03b2 production in the anterior chamber. In concert, an autocrine prostaglandin circuit mediated canonical rapid IOP lowering. This work reveals parallel mechanisms underlying acute and long-term latanoprost activities during glaucoma treatment.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.192010","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T17:00:33Z","timestamp":1771952433000},"source":"Crossref","is-referenced-by-count":4,"title":["Lipidomic analysis reveals drug-induced lipoxin synthesis in glaucoma treatment"],"prefix":"10.1172","volume":"11","author":[{"given":"David J.","family":"Mathew","sequence":"first","affiliation":[{"name":"Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, Canada."},{"name":"Department of Ophthalmology and Vision Science, and"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto School of Medicine, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubham","family":"Maurya","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Optometry & Vision Science, and"},{"name":"Vision Science Program, University of California Berkeley, Berkeley, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Ho","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Optometry & Vision Science, and"},{"name":"Vision Science Program, University of California Berkeley, Berkeley, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izhar","family":"Livne-Bar","sequence":"additional","affiliation":[{"name":"Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, Canada."},{"name":"Department of Ophthalmology and Vision Science, and"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto School of Medicine, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Chan","sequence":"additional","affiliation":[{"name":"Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, Canada."},{"name":"Department of Ophthalmology and Vision Science, and"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto School of Medicine, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny Wanyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, Canada."},{"name":"Department of Ophthalmology and Vision Science, and"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto School of Medicine, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne M.","family":"Buys","sequence":"additional","affiliation":[{"name":"Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, Canada."},{"name":"Department of Ophthalmology and Vision Science, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Sit","sequence":"additional","affiliation":[{"name":"Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, Canada."},{"name":"Department of Ophthalmology and Vision Science, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Trope","sequence":"additional","affiliation":[{"name":"Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, Canada."},{"name":"Department of Ophthalmology and Vision Science, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Peters","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine, and"},{"name":"Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Optometry & Vision Science, and"},{"name":"Vision Science Program, University of California Berkeley, Berkeley, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Gronert","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Optometry & Vision Science, and"},{"name":"Vision Science Program, University of California Berkeley, Berkeley, California, USA."},{"name":"Infectious Disease and Immunity Program, University of California Berkeley, Berkeley, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8776-223X","authenticated-orcid":true,"given":"Jeremy M.","family":"Sivak","sequence":"additional","affiliation":[{"name":"Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, Canada."},{"name":"Department of Ophthalmology and Vision Science, and"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto School of Medicine, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2018.11.005"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.67"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.05.013"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164876"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/IJG.0000000000001906"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6701674"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)62111-5"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2015.10.053"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.11686"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2008.08.010"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2013.0179"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1089\/10807680260218489"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.119.8.1165"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.3.15"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3109\/13816810.2016.1164193"},{"issue":"13","key":"B16","first-page":"2772","article-title":"Prostaglandins increase matrix metalloproteinase release from human ciliary smooth muscle cells","volume":"38","author":"Weinreb","year":"1997","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-01248-0"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2024.106815"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1177\/20420986241285929"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/aos.15725"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2020.02.004"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-1703-1"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.629907"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1124\/mi.8.1.7"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nature13479"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03010-0"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2017.03.006"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI77398"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201801076"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202200360"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-024-01767-2"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-024-00775-z"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53294-4"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.21.9475"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.223883"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2009.141"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.03.083"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3911"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2024.108753"},{"issue":"11","key":"B40","first-page":"2144","article-title":"Antiinflammatory mediator lipoxin A4 and its receptor in synovitis of patients with rheumatoid arthritis","volume":"34","author":"Hashimoto","year":"2007","journal-title":"J Rheumatol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.11.010"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.6061\/clinics\/2014(04)09"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-011-9311-2"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109382109"},{"key":"B45","first-page":"534","article-title":"Alterations in gene expression induced by cyclic mechanical stress in trabecular meshwork cells","volume":"15","author":"Luna","year":"2009","journal-title":"Mol Vis"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25181-7"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.29578"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20030"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-02057-w"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/89759"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1410851111"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0142848"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-015-0165-4"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.2174\/1381612043453144"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1185\/030079906X112471"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S86971"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2016-308505"},{"issue":"13","key":"B58","first-page":"3193","article-title":"Mechanisms of action of unoprostone on trabecular meshwork contractility","volume":"42","author":"Thieme","year":"2001","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0990"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1097\/IJG.0b013e31802fc6d3"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(89)90011-0"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-003-0835-1"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1996.0119"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2005.080895"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1159\/000333822"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81048-3"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1274-7"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27044"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1097\/IJG.0000000000000627"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.07.011"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108019"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01624-9"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-90696-4"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1021\/ab500060r"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3390\/biom12091231"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004169107"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/0039-6257(79)90229-7"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2019.02.014"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.11227"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042627"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-11067"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2021.100117"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001571"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1038\/nature11351"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1080\/08164622.2022.2083945"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1097\/IJG.0000000000000603"},{"issue":"1","key":"B87","first-page":"151","article-title":"In vitro localization of TIGR\/MYOC in trabecular meshwork extracellular matrix and binding to fibronectin","volume":"43","author":"Filla","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3390\/cells12030504"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0626"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2018.03.001"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/192010\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:16:23Z","timestamp":1778872583000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/192010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,24]]},"references-count":91,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,2,19]]},"published-print":{"date-parts":[[2026,4,8]]}},"alternative-id":["10.1172\/jci.insight.192010"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.192010","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,24]]},"article-number":"e192010"}}