{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:35:00Z","timestamp":1793054100945,"version":"4.5.0"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-15-00123"],"award-info":[{"award-number":["21-15-00123"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Primary open-angle glaucoma (POAG) is characterized by degeneration of retinal ganglion cells associated with an increase in intraocular pressure (IOP) due to hindered aqueous humor (AH) drainage through the trabecular meshwork and uveoscleral pathway. Polyunsaturated fatty acids and oxylipins are signaling lipids regulating neuroinflammation, neuronal survival and AH outflow. Among them, prostaglandins have been previously implicated in glaucoma and employed for its treatment. This study addressed the role of signaling lipids in glaucoma by determining their changes in AH accompanying IOP growth and progression of the disease. Eye liquids were collected from patients with POAG of different stages and cataract patients without glaucoma. Lipids were identified and quantified by UPLC-MS\/MS. The compounds discriminating glaucoma groups were recognized using ANCOVA and PLS-DA statistic approaches and their biosynthetic pathways were predicted by bioinformatics. Among 22 signaling lipids identified in AH, stage\/IOP-dependent alterations in glaucoma were provided by a small set of mediators, including 12,13-DiHOME, 9- and 13-HODE\/KODE, arachidonic acid and lyso-PAF. These observations correlated with the expression of cytochromes P450 (CYPs) and phospholipases A2 in the ocular tissues. Interestingly, tear fluid exhibited similar lipidomic alterations in POAG. Overall, POAG may involve arachidonic acid\/PAF-dependent pathways and oxidative stress as evidenced from an increase in its markers, KODEs and 12,13-DiHOME. The latter is a product of CYPs, one of which, CYP1B1, is known as POAG and primary congenital glaucoma-associated gene. These data provide novel targets for glaucoma treatment. Oxylipin content of tear fluid may have diagnostic value in POAG.<\/jats:p>","DOI":"10.3390\/biology10070658","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T22:25:31Z","timestamp":1626215131000},"page":"658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Targeted Lipidomic Analysis of Aqueous Humor Reveals Signaling Lipid-Mediated Pathways in Primary Open-Angle Glaucoma"],"prefix":"10.3390","volume":"10","author":[{"given":"Nadezhda V.","family":"Azbukina","sequence":"first","affiliation":[{"name":"Faculty of Bioengineering and Bioinformatics, Moscow Lomonosov State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry V.","family":"Chistyakov","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei V.","family":"Goriainov","sequence":"additional","affiliation":[{"name":"SREC PFUR, Peoples\u2019 Friendship University of Russia, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav I.","family":"Kotelin","sequence":"additional","affiliation":[{"name":"Helmholtz National Medical Research Center of Eye Diseases, 105062 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V.","family":"Fedoseeva","sequence":"additional","affiliation":[{"name":"Helmholtz National Medical Research Center of Eye Diseases, 105062 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6922-0464","authenticated-orcid":false,"given":"Sergey Yu.","family":"Petrov","sequence":"additional","affiliation":[{"name":"Helmholtz National Medical Research Center of Eye Diseases, 105062 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina G.","family":"Sergeeva","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8143-3606","authenticated-orcid":false,"given":"Elena N.","family":"Iomdina","sequence":"additional","affiliation":[{"name":"Helmholtz National Medical Research Center of Eye Diseases, 105062 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3013-7863","authenticated-orcid":false,"given":"Evgeni Yu.","family":"Zernii","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1001\/jama.2014.3192","article-title":"The Pathophysiology and Treatment of Glaucoma","volume":"311","author":"Weinreb","year":"2014","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1080\/09286580701501931","article-title":"Open-Angle Glaucoma\u2014An Epidemiologic Overview","volume":"14","author":"Leske","year":"2007","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_3","first-page":"623","article-title":"Alterations in proteome of human sclera associated with primary open-angle glaucoma involve proteins participating in regulation of the extracellular matrix","volume":"26","author":"Iomdina","year":"2020","journal-title":"Mol. Vis."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1442-9071.2006.01146.x","article-title":"Possible role of excitotoxicity in the pathogenesis of glaucoma","volume":"34","author":"Casson","year":"2006","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_6","first-page":"E209","article-title":"Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration","volume":"114","author":"Li","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S144","DOI":"10.1016\/j.survophthal.2007.08.010","article-title":"What Is the Link Between Vascular Dysregulation and Glaucoma?","volume":"52","author":"Grieshaber","year":"2007","journal-title":"Surv. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.survophthal.2012.08.010","article-title":"The Role of Inflammation in the Pathogenesis of Glaucoma","volume":"58","author":"Vohra","year":"2013","journal-title":"Surv. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3945\/an.114.007732","article-title":"Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs","volume":"6","author":"Gabbs","year":"2015","journal-title":"Adv. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/946813","article-title":"Role of Prostaglandins in Neuroinflammatory and Neurodegenerative Diseases","volume":"2012","author":"Lima","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_11","first-page":"1","article-title":"Prostaglandins as the Agents That Modulate the Course of Brain Disorders","volume":"10","author":"Famitafreshi","year":"2020","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_12","first-page":"1835","article-title":"Protective effect of arachidonic acid on glutamate neurotoxicity in rat retinal ganglion cells","volume":"43","author":"Kawasaki","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Brust, A.-K., Ulbrich, H.K., Seigel, G.M., Pfeiffer, N., and Grus, F.H. (2008). Effects of Cyclooxygenase Inhibitors on Apoptotic Neuroretinal Cells. Biomark. Insights, 3.","DOI":"10.4137\/BMI.S692"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.neures.2009.08.008","article-title":"Cyclooxygenase-2 plays a critical role in retinal ganglion cell death after transient ischemia: Real-time monitoring of RGC survival using Thy-1-EGFP transgenic mice","volume":"65","author":"Sakai","year":"2009","journal-title":"Neurosci. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3109\/13816810.2016.1164193","article-title":"Prostaglandins in the eye: Function, expression, and roles in glaucoma","volume":"38","author":"Doucette","year":"2016","journal-title":"Ophthalmic Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/0014-4835(88)90043-7","article-title":"Morphological study of the anterior segment of cynomolgus monkey eyes following treatment with prostaglandin F2\u03b1","volume":"47","author":"Tamm","year":"1988","journal-title":"Exp. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/00055735-200004000-00008","article-title":"The mechanism of action of prostaglandins on uveoscleral outflow","volume":"11","author":"Schachtschabel","year":"2000","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1089\/jop.2014.0067","article-title":"Pharmacotherapy of Glaucoma","volume":"31","author":"Schmidl","year":"2015","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_19","first-page":"349","article-title":"Glaucoma and the Applications of Carbonic Anhydrase Inhibitors","volume":"75","author":"Scozzafava","year":"2014","journal-title":"Alzheimer\u2019s Disease"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1038\/s41598-018-36952-6","article-title":"Comprehensive measurements of hydroxylinoleate and hydroxyarachidonate isomers in blood samples from primary open-angle glaucoma patients and controls","volume":"9","author":"Umeno","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"52","DOI":"10.2174\/1874364101004010052","article-title":"Aqueous Humor Dynamics: A Review","volume":"4","author":"Goel","year":"2010","journal-title":"Open Ophthalmol. J."},{"key":"ref_22","doi-asserted-by":"crossref","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":"ref_23","doi-asserted-by":"crossref","first-page":"108024","DOI":"10.1016\/j.exer.2020.108024","article-title":"Differentiation of soluble aqueous humor metabolites in primary open angle glaucoma and controls","volume":"194","author":"Myer","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s11306-020-1650-y","article-title":"Comparative lipidomic analysis of inflammatory mediators in the aqueous humor and tear fluid of humans and rabbits","volume":"16","author":"Chistyakov","year":"2020","journal-title":"Metabolomics"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chistyakov, D.V., Gancharova, O.S., Baksheeva, V.E., Tiulina, V.V., Goriainov, S.V., Azbukina, N.V., Tsarkova, M.S., Zamyatnin, J.A.A., Philippov, P.P., and Sergeeva, M.G. (2020). Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms. Biomedicines, 8.","DOI":"10.3390\/biomedicines8090344"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chistyakov, D.V., Baksheeva, V.E., Tiulina, V.V., Goriainov, S.V., Azbukina, N.V., Gancharova, O.S., Arifulin, E.A., Komarov, S.V., Chistyakov, V.V., and Tikhomirova, N.K. (2020). Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030704"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1039\/C1MB05357D","article-title":"Differential protein expression in tears of patients with primary open angle and pseudoexfoliative glaucoma","volume":"8","author":"Pieragostino","year":"2012","journal-title":"Mol. BioSyst."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1039\/c3mb25463a","article-title":"Shotgun proteomics reveals specific modulated protein patterns in tears of patients with primary open angle glaucoma na\u00efve to therapy","volume":"9","author":"Pieragostino","year":"2013","journal-title":"Mol. BioSyst."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4225","DOI":"10.2174\/0929867325666181009153212","article-title":"Structural and Molecular Tear Film Changes in Glaucoma","volume":"26","author":"Mastropasqua","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_30","unstructured":"Egorov, E., Astakhov, Y., and Shuko, A. (2011). National Glaucoma Guidelines, GEOTAR Media."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s11306-007-0070-6","article-title":"The metabolomics standards initiative (MSI)","volume":"3","author":"Fiehn","year":"2007","journal-title":"Metabolomics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.12688\/f1000research.7563.2","article-title":"Differential analyses for RNA-seq: Transcript-level estimates improve gene-level inferences","volume":"4","author":"Soneson","year":"2016","journal-title":"F1000Research"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Stocchero, M., Locci, E., D\u2019Aloja, E., Nioi, M., Baraldi, E., and Giordano, G. (2019). PLS2 in Metabolomics. Metabolites, 9.","DOI":"10.3390\/metabo9030051"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.ajo.2006.02.014","article-title":"LXII Edward Jackson Lecture: Open Angle Glaucoma after Vitrectomy","volume":"141","author":"Chang","year":"2006","journal-title":"Am. J. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1002\/jcb.29578","article-title":"Transcriptome-wide study of the response of human trabecular meshwork cells to the substrate stiffness increase","volume":"121","author":"Tie","year":"2020","journal-title":"J. Cell. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-12858-7","article-title":"Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes","volume":"7","author":"Mirzaei","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"29759","DOI":"10.1038\/srep29759","article-title":"Glaucoma related Proteomic Alterations in Human Retina Samples","volume":"6","author":"Funke","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1167\/iovs.17-22759","article-title":"Biomechanical Rigidity and Quantitative Proteomics Analysis of Segmental Regions of the Trabecular Meshwork at Physiologic and Elevated Pressures","volume":"59","author":"Vranka","year":"2018","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3856","DOI":"10.1111\/jcmm.14975","article-title":"Endogenous ocular lipids as potential modulators of intraocular pressure","volume":"24","author":"Edwards","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1097\/IJG.0000000000000603","article-title":"Changes in the Lipidomic Profile of Aqueous Humor in Open-Angle Glaucoma","volume":"26","author":"Cabrerizo","year":"2017","journal-title":"J. Glaucoma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.18097\/PBMC20196501033","article-title":"Inflammatory metabolites of arahidonic acid in tear fluid in UV-induced corneal damage","volume":"65","author":"Chistyakov","year":"2019","journal-title":"Biomeditsinskaya Khimiya"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/nm.4297","article-title":"The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue","volume":"23","author":"Lynes","year":"2017","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.cmet.2018.03.020","article-title":"12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake","volume":"27","author":"Stanford","year":"2018","journal-title":"Cell Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1007\/s00204-017-2060-4","article-title":"Beyond detoxification: A role for mouse mEH in the hepatic metabolism of endogenous lipids","volume":"91","author":"Marowsky","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"28736","DOI":"10.1038\/srep28736","article-title":"Transcriptome profiling of the rat retina after optic nerve transection","volume":"6","author":"Yasuda","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev.pharmtox.48.061807.154729","article-title":"Role of CYP1B1 in Glaucoma","volume":"48","author":"Vasiliou","year":"2008","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1159\/000485089","article-title":"Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species","volume":"44","author":"He","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"108484","DOI":"10.1016\/j.jnutbio.2020.108484","article-title":"Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: A review of recent studies","volume":"86","author":"Hildreth","year":"2020","journal-title":"J. Nutr. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"R68","DOI":"10.1152\/ajpregu.00092.2014","article-title":"Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling","volume":"307","author":"Nieman","year":"2014","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1177\/2042018810375656","article-title":"Review: Hydroxyoctadecadienoic acids: Novel regulators of macrophage differentiation and atherogenesis","volume":"1","author":"Vangaveti","year":"2010","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.freeradbiomed.2019.12.011","article-title":"Involvement of free radical-mediated oxidation in the pathogenesis of pseudoexfoliation syndrome detected based on specific hydroxylinoleate isomers","volume":"147","author":"Umeno","year":"2020","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_54","first-page":"27","article-title":"CYP1B1: A key regulator of redox homeostasis","volume":"13","author":"Song","year":"2018","journal-title":"Trends Cell Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.mrrev.2005.11.001","article-title":"The role of oxidative stress in glaucoma","volume":"612","author":"Izzotti","year":"2006","journal-title":"Mutat. Res. Mutat. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Yamashita, A., Hayashi, Y., Matsumoto, N., Nemoto-Sasaki, Y., Koizumi, T., Inagaki, Y., Oka, S., Tanikawa, T., and Sugiura, T. (2017). Coenzyme-A-Independent Transacylation System; Possible Involvement of Phospholipase A2 in Transacylation. Biology, 6.","DOI":"10.3390\/biology6020023"},{"key":"ref_57","first-page":"408","article-title":"Phospholipase A2 in chamber angle of normal eyes and patients with primary open angle glaucoma and exfoliation glaucoma","volume":"13","author":"Rekonen","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s00417-007-0757-4","article-title":"Phospholipases A2 in normal human conjunctiva and from patients with primary open-angle glaucoma and exfoliation glaucoma","volume":"246","author":"Helin","year":"2008","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1001\/archopht.1991.01080030112049","article-title":"Synthesis of Platelet Activating Factor by Ocular Tissue From Inflamed Eyes","volume":"109","author":"Rosenbaum","year":"1991","journal-title":"Arch. Ophthalmol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1016\/S0039-6257(97)80004-5","article-title":"Signal transduction and gene expression in the eye: A contemporary view of the pro-inflammatory, anti-inflammatory and modulatory roles of prostaglandins and other bioactive lipids","volume":"41","author":"Bazan","year":"1997","journal-title":"Surv. Ophthalmol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0090-6980(93)90093-M","article-title":"Antagonist of platelet-activating factor prevents prostaglandin E2 induced ocular hypertension in rabbits","volume":"45","author":"Jager","year":"1993","journal-title":"Prostaglandins"},{"key":"ref_62","first-page":"1048","article-title":"Platelet-Activating-Factor (Paf) Enhances Glutamic-Acid Release in the Retina through a Presynaptic Receptor","volume":"34","author":"Marcheselli","year":"1993","journal-title":"Investig. Ophth. Vis. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.2147\/DDDT.S117806","article-title":"Impact of prostaglandin glaucoma drops on platelet-activating factor action: An in vitro study","volume":"10","author":"Moschos","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3389\/fphar.2019.00095","article-title":"Soluble Epoxide Hydrolase Inhibition for Ocular Diseases: Vision for the Future","volume":"10","author":"Park","year":"2019","journal-title":"Front. Pharmacol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/7\/658\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:29:42Z","timestamp":1760164182000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/7\/658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,13]]},"references-count":64,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["biology10070658"],"URL":"https:\/\/doi.org\/10.3390\/biology10070658","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,13]]}}}