{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T04:40:36Z","timestamp":1759207236758,"version":"3.44.0"},"reference-count":71,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008792","name":"Novartis Pharma GmbH","doi-asserted-by":"crossref","award":["MRTH258A_FVMI006"],"award-info":[{"award-number":["MRTH258A_FVMI006"]}],"id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Purpose: This study sets out to analyze the correlation of ET-1, a vasoactive peptide, along with various cytokines and vascular factors, with clinical parameters and OCT\/OCT-A measurements in glaucoma participants. Methods: Eyes of participants with cataract (n = 30) or glaucoma (n = 87) were examined with optical coherence tomography (OCT) and OCT angiography (OCT-A). Aqueous humor (AqH) from the examined eye and plasma were sampled during cataract or glaucoma surgery and analyzed by means of ELISA and Luminex assay to determine their levels of ET-1 and 35 proteins deemed relevant for regulation of the AqH outflow pathway, ocular perfusion (OP), and glucose metabolism. Results: Glaucomatous eyes are characterized by reductions in RNFL thickness and OP, reflected by reduced vessel density. Furthermore, significantly elevated peripheral ET-1 levels were detected in participants with glaucoma. In addition, significantly elevated AqH levels of MMP-2, MMP-3, ET-1, sEMMPRIN, ZAG, sLOX-1, follistatin, cortisol, endostatin, sTIE-2, and PDGF-BB were detected in the glaucomatous eyes, with correlation to reduced VD for APN, C3a, MMP-3, resistin, sTIE-2, and ZAG. Multivariable analysis showed a correlation of AqH APN levels with the reduced VD in glaucomatous eyes. Conclusions: The peripheral ET-1 level and the intraocular levels of APN, C3a, MMP-3, resistin, sTIE-2, and ZAG are associated with impaired OP in glaucoma. Furthermore, elevated intraocular levels of MMP-3, ZAG, and APN were identified as biomarkers for impaired perfusion in glaucoma.<\/jats:p>","DOI":"10.3390\/biom15101364","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T06:02:52Z","timestamp":1758866572000},"page":"1364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ET-1, MMPs, ZAG, and APN Link Reduced Ocular Perfusion to Glaucoma"],"prefix":"10.3390","volume":"15","author":[{"given":"Maren","family":"Kasper","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Ophtha-Lab at St. Franziskus-Hospital, 48145 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-8795","authenticated-orcid":false,"given":"Kai","family":"Rothaus","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Ophtha-Lab at St. Franziskus-Hospital, 48145 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-157X","authenticated-orcid":false,"given":"Lasse","family":"Schopmeyer","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Erasmus Medical Center (EMC), 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Ophtha-Lab at St. Franziskus-Hospital, 48145 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swaantje","family":"Grisanti","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2814-4327","authenticated-orcid":false,"given":"Carsten","family":"Heinz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Ophtha-Lab at St. Franziskus-Hospital, 48145 Muenster, Germany"},{"name":"Department of Ophthalmology, University of Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Loser","sequence":"additional","affiliation":[{"name":"Department of Human Medicine, University of Oldenburg, 26129 Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9358-249X","authenticated-orcid":false,"given":"Claudia","family":"Lommatzsch","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Ophtha-Lab at St. Franziskus-Hospital, 48145 Muenster, Germany"},{"name":"Department of Ophthalmology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ajo.2012.02.024","article-title":"The Changing Face of Primary Open-Angle Glaucoma in the United States: Demographic and Geographic Changes from 2011 to 2050","volume":"154","author":"Vajaranant","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"ref_2","first-page":"e11686","article-title":"Epidemiology of Glaucoma: The Past, Present, and Predictions for the Future","volume":"12","author":"Allison","year":"2020","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1001\/jama.2014.3192","article-title":"The Pathophysiology and Treatment of Glaucoma: A Review","volume":"311","author":"Weinreb","year":"2014","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.preteyeres.2007.08.001","article-title":"A Framework for Comparing Structural and Functional Measures of Glaucomatous Damage","volume":"26","author":"Hood","year":"2007","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6939","DOI":"10.1167\/iovs.12-10345","article-title":"The Structure and Function Relationship in Glaucoma: Implications for Detection of Progression and Measurement of Rates of Change","volume":"53","author":"Medeiros","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1167\/iovs.12-11026","article-title":"Progressive Loss of Retinal Ganglion Cell Function Precedes Structural Loss by Several Years in Glaucoma Suspects","volume":"54","author":"Banitt","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1167\/tvst.11.8.3","article-title":"Long-and Short-Term Variability of Perimetry in Glaucoma","volume":"11","author":"Gardiner","year":"2022","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0161-6420(02)01564-6","article-title":"Optical Coherence Tomography Measurement of Macular and Nerve Fiber Layer Thickness in Normal and Glaucomatous Human Eyes","volume":"110","author":"Guedes","year":"2003","journal-title":"Ophthalmology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6344","DOI":"10.1167\/iovs.15-17248","article-title":"Residual and Dynamic Range of Retinal Nerve Fiber Layer Thickness in Glaucoma: Comparison of Three OCT Platforms","volume":"56","author":"Mwanza","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_10","first-page":"2340","article-title":"Nitric Oxide and Endothelin-1 Are Important Regulators of Human Ophthalmic Artery","volume":"33","author":"Haefliger","year":"1992","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00417-019-04239-9","article-title":"Is Primary Open-Angle Glaucoma an Ocular Manifestation of Systemic Disease?","volume":"257","author":"Wey","year":"2019","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol. Albrecht Von Graefes Arch. Klin. Exp. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1364\/BOE.3.003127","article-title":"Quantitative OCT Angiography of Optic Nerve Head Blood Flow","volume":"3","author":"Jia","year":"2012","journal-title":"Biomed. Opt. Express"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lommatzsch, C., Rothaus, K., Schopmeyer, L., Feldmann, M., Bauer, D., Grisanti, S., Heinz, C., and Kasper, M. (2022). Elevated Endothelin-1 Levels as Risk Factor for an Impaired Ocular Blood Flow Measured by OCT-A in Glaucoma. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-15401-5"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s00417-018-3965-1","article-title":"OCTA Vessel Density Changes in the Macular Zone in Glaucomatous Eyes","volume":"256","author":"Lommatzsch","year":"2018","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol. Albrecht Von Graefes Arch. Klin. Exp. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rao, H.L., Pradhan, Z.S., Weinreb, R.N., Riyazuddin, M., Dasari, S., Venugopal, J.P., Puttaiah, N.K., Rao, D.A.S., Devi, S., and Mansouri, K. (2017). A Comparison of the Diagnostic Ability of Vessel Density and Structural Measurements of Optical Coherence Tomography in Primary Open Angle Glaucoma. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173930"},{"key":"ref_16","first-page":"835","article-title":"Vessel Density in OCT Angiography Permits Differentiation between Normal and Glaucomatous Optic Nerve Heads","volume":"11","author":"Lommatzsch","year":"2018","journal-title":"Int. J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1136\/bjo.2004.046755","article-title":"Increased Plasma Endothelin-1 Levels in Patients with Progressive Open Angle Glaucoma","volume":"89","author":"Emre","year":"2005","journal-title":"Br. J. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.lfs.2012.02.013","article-title":"Endothelin-1 Plasma Levels and Vascular Endothelial Dysfunction in Primary Open Angle Glaucoma","volume":"91","author":"Cellini","year":"2012","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1139\/Y10-036","article-title":"ET-1 Plasma Levels and Ocular Blood Flow in Retinitis Pigmentosa","volume":"88","author":"Cellini","year":"2010","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/eye.2017.74","article-title":"Aqueous Humor Endothelin-1 and Total Retinal Blood Flow in Patients with Non-Proliferative Diabetic Retinopathy","volume":"31","author":"Khuu","year":"2017","journal-title":"Eye"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.2147\/OPTH.S155551","article-title":"Retrobulbar Hemodynamics and Aqueous Humor Levels of Endothelin-1 in Exfoliation Syndrome and Exfoliation Glaucoma","volume":"12","author":"Koukoula","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1006\/exer.1994.1158","article-title":"Aqueous Humor in Glaucomatous Eyes Contains an Increased Level of TGF-Beta 2","volume":"59","author":"Tripathi","year":"1994","journal-title":"Exp. Eye Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nga, A.D.C., Yap, S.-L., Samsudin, A., Abdul-Rahman, P.S., Hashim, O.H., and Mimiwati, Z. (2014). Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in the Aqueous Humour of Patients with Primary Angle Closure Glaucoma\u2014A Quantitative Study. BMC Ophthalmol., 14.","DOI":"10.1186\/1471-2415-14-33"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1167\/iovs.02-0365","article-title":"Matrix Metalloproteinases and Their Inhibitors in Aqueous Humor of Patients with Pseudoexfoliation Syndrome\/Glaucoma and Primary Open-Angle Glaucoma","volume":"44","author":"Lommatzsch","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.4103\/1673-5374.355765","article-title":"Ocular Manifestations of Central Insulin Resistance","volume":"18","author":"Faiq","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/ojo.OJO_91_2018","article-title":"A Glimpse into the Mysteries of Glaucoma: From Theories to Clinics","volume":"12","author":"Faiq","year":"2019","journal-title":"Oman J. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.mehy.2014.02.005","article-title":"Glaucoma\u2013Diabetes of the Brain: A Radical Hypothesis about Its Nature and Pathogenesis","volume":"82","author":"Faiq","year":"2014","journal-title":"Med. Hypotheses"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"46","DOI":"10.2174\/1566524017666170206153415","article-title":"Diabetes Type 4: A Paradigm Shift in the Understanding of Glaucoma, the Brain Specific Diabetes and the Candidature of Insulin as a Therapeutic Agent","volume":"17","author":"Faiq","year":"2017","journal-title":"Curr. Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.oret.2025.01.015","article-title":"Standardization of OCT Angiography Nomenclature in Retinal Vascular Diseases: Consensus-Based Recommendations","volume":"9","author":"Munk","year":"2025","journal-title":"Ophthalmol. Retina"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/eye.2017.159","article-title":"OCT Glaucoma Staging System: A New Method for Retinal Nerve Fiber Layer Damage Classification Using Spectral-Domain OCT","volume":"32","author":"Brusini","year":"2018","journal-title":"Eye"},{"key":"ref_31","unstructured":"McFadden, D. (1974). Conditional Logit Analysis of Qualitative Choice Behavior. Frontiers in Econometrics, Academic Press."},{"key":"ref_32","first-page":"1","article-title":"mice: Multivariate Imputation by Chained Equations in R","volume":"45","year":"2011","journal-title":"J. Stat. Softw."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization Paths for Generalized Linear Models via Coordinate Descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J. Stat. Softw."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v106.i01","article-title":"Elastic Net Regularization Paths for All Generalized Linear Models","volume":"106","author":"Tay","year":"2023","journal-title":"J. Stat. Softw."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Methodol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S115","DOI":"10.1016\/j.survophthal.2007.08.005","article-title":"Does the Blood-Brain Barrier Play a Role in Glaucoma?","volume":"52","author":"Grieshaber","year":"2007","journal-title":"Surv. Ophthalmol."},{"key":"ref_37","first-page":"925","article-title":"Analyzing Cytokines as Biomarkers to Evaluate Severity of Glaucoma","volume":"10","author":"Tong","year":"2017","journal-title":"Int. J. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3833","DOI":"10.19082\/3833","article-title":"Levels of Cytokines in the Aqueous Humor of Eyes with Primary Open Angle Glaucoma, Pseudoexfoliation Glaucoma and Cataract","volume":"9","author":"Khalef","year":"2017","journal-title":"Electron. Physician"},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1159\/000323584","article-title":"Endothelin-1 and Nitric Oxide Levels in Patients with Glaucoma","volume":"46","author":"Ghanem","year":"2011","journal-title":"Ophthalmic Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/00061198-200206000-00016","article-title":"Endothelin: Is It a Contributor to Glaucoma Pathophysiology?","volume":"11","author":"Yorio","year":"2002","journal-title":"J. Glaucoma"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.niox.2018.04.010","article-title":"The Nitric Oxide-Guanylate Cyclase Pathway and Glaucoma","volume":"77","author":"Wareham","year":"2018","journal-title":"Nitric Oxide Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/02713683.2011.622849","article-title":"Endothelin and Its Suspected Role in the Pathogenesis and Possible Treatment of Glaucoma","volume":"37","author":"Shoshani","year":"2012","journal-title":"Curr. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s40123-017-0094-6","article-title":"A Review of Nitric Oxide for the Treatment of Glaucomatous Disease","volume":"6","author":"Aliancy","year":"2017","journal-title":"Ophthalmol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9944","DOI":"10.1073\/pnas.96.17.9944","article-title":"Inhibition of Nitric-Oxide Synthase 2 by Aminoguanidine Provides Neuroprotection of Retinal Ganglion Cells in a Rat Model of Chronic Glaucoma","volume":"96","author":"Neufeld","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1139\/Y08-040","article-title":"Role of the ETB Receptor in Retinal Ganglion Cell Death in Glaucoma","volume":"86","author":"Krishnamoorthy","year":"2008","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.ajpath.2011.05.036","article-title":"EMMPRIN Modulates Epithelial Barrier Function through a MMP-Mediated Occludin Cleavage: Implications in Dry Eye Disease","volume":"179","author":"Huet","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kim, M.H., and Lim, S.-H. (2022). Matrix Metalloproteinases and Glaucoma. Biomolecules, 12.","DOI":"10.3390\/biom12101368"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1167\/iovs.04-0832","article-title":"Retinal Ganglion Cell Apoptosis in Glaucoma Is Related to Intraocular Pressure and IOP-Induced Effects on Extracellular Matrix","volume":"46","author":"Guo","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1089\/jop.2019.0146","article-title":"Matrix Metalloproteinases and Glaucoma Treatment","volume":"36","author":"Weinreb","year":"2020","journal-title":"J. Ocul. Pharmacol. Ther. Off. J. Assoc. Ocul. Pharmacol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/01.ijg.0000145812.39224.0a","article-title":"Matrix Metalloproteinases and Their Tissue Inhibitors in Aqueous Humor of Patients with Primary Open-Angle Glaucoma, Exfoliation Syndrome, and Exfoliation Glaucoma","volume":"14","author":"Tervahartiala","year":"2005","journal-title":"J. Glaucoma"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Moli\u00e8re, S., Jaulin, A., Tomasetto, C.-L., and Dali-Youcef, N. (2023). Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Metabolism: Insights into Health and Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310649"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s004170000241","article-title":"Transforming Growth Factor-Beta 2 Levels in Aqueous Humor of Glaucomatous Eyes","volume":"239","author":"Inatani","year":"2001","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol. Albrecht Von Graefes Arch. Klin. Exp. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7358","DOI":"10.1167\/iovs.12-10292","article-title":"The Effects of Transforming Growth Factor-\u03922 on the Expression of Follistatin and Activin A in Normal and Glaucomatous Human Trabecular Meshwork Cells and Tissues","volume":"53","author":"Fitzgerald","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1089\/jop.2013.0220","article-title":"The Role of TGF-\u03922 and Bone Morphogenetic Proteins in the Trabecular Meshwork and Glaucoma","volume":"30","author":"Wordinger","year":"2014","journal-title":"J. Ocul. Pharmacol. Ther. Off. J. Assoc. Ocul. Pharmacol. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0092-8674(00)81848-6","article-title":"Endostatin: An Endogenous Inhibitor of Angiogenesis and Tumor Growth","volume":"88","author":"Boehm","year":"1997","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1016\/S0042-6989(98)00037-6","article-title":"Platelet-Derived Growth Factor B-Chain Expression in the Rat Retina and Optic Nerve: Distribution and Changes after Transection of the Optic Nerve","volume":"38","author":"Mekada","year":"1998","journal-title":"Vis. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1093\/eurjhf\/hft117","article-title":"Circulating Angiopoietin-2, Its Soluble Receptor Tie-2, and Mortality in the General Population","volume":"15","author":"Lorbeer","year":"2013","journal-title":"Eur. J. Heart Fail."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"572","DOI":"10.5551\/jat.36327","article-title":"Association of the LOX-1 Rs1050283 Polymorphism with Risk for Atherosclerotic Cerebral Infarction and Its Effect on sLOX-1 and LOX-1 Expression in a Chinese Population","volume":"24","author":"Guo","year":"2017","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Kott, K.A., Genetzakis, E., Gray, M.P., Hansen, P., McGuire, H.M., Yang, J.Y., Grieve, S.M., Vernon, S.T., and Figtree, G.A. (2023). Serum Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor-1 (sLOX-1) Is Associated with Atherosclerosis Severity in Coronary Artery Disease. Biomolecules, 13.","DOI":"10.3390\/biom13081187"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"108460","DOI":"10.1016\/j.exer.2021.108460","article-title":"Increased Ratios of Complement Factors C3a to C3 in Aqueous Humor and Serum Mark Glaucoma Progression","volume":"204","author":"Hubens","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3109\/02713688109019976","article-title":"Aqueous Humour and Plasma Cortisol Levels in Glaucoma and Cataract Patients","volume":"1","author":"Hampl","year":"1981","journal-title":"Curr. Eye Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1172\/JCI29126","article-title":"Adiponectin and Adiponectin Receptors in Insulin Resistance, Diabetes, and the Metabolic Syndrome","volume":"116","author":"Kadowaki","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3892\/br.2017.953","article-title":"Nitric Oxide\/Cyclic GMP Pathway Mediates the Endothelin-1-Upregulation of Adiponectin Expression in Rat Cardiomyocytes","volume":"7","author":"Guo","year":"2017","journal-title":"Biomed. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1530\/EJE-15-0637","article-title":"Effects of Sitagliptin on Circulating Zinc-A2-Glycoprotein Levels in Newly Diagnosed Type 2 Diabetes Patients: A Randomized Trial","volume":"174","author":"Tian","year":"2016","journal-title":"Eur. J. Endocrinol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Banaszak, M., G\u00f3rna, I., and Przys\u0142awski, J. (2021). Zinc and the Innovative Zinc-A2-Glycoprotein Adipokine Play an Important Role in Lipid Metabolism: A Critical Review. Nutrients, 13.","DOI":"10.3390\/nu13062023"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Sp\u00f6rri, L., Uldry, A.-C., Kreuzer, M., Herzog, E.L., Zinkernagel, M.S., Unterlauft, J.D., and Zysset-Burri, D.C. (2024). Exploring the Ocular Surface Microbiome and Tear Proteome in Glaucoma. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116257"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"100059","DOI":"10.1016\/j.endmts.2020.100059","article-title":"Circulating Resistin Levels in Relation with Insulin Resistance, Inflammatory and Endothelial Dysfunction Markers in Patients with Type 2 Diabetes and Impaired Fasting Glucose","volume":"1","author":"Siddiqui","year":"2020","journal-title":"Endocr. Metab. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1080\/09273948.2019.1609049","article-title":"Alteration of MCP-1 and MMP-9 in Aqueous Humor Is Associated with Secondary Glaucoma in Fuchs Uveitis Syndrome","volume":"28","author":"Bauer","year":"2020","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_70","first-page":"302","article-title":"Neuroprotective Effects of Anti-Diabetic Drugs in the Treatment of Patients with Diabetes and Glaucoma or at High Risk for Glaucoma","volume":"241","author":"Weisser","year":"2024","journal-title":"Klin. Monatsbl. Augenheilkd."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Bojikian, K.D., Chen, C.L., Wen, J.C., Zhang, Q., Xin, C., Gupta, D., Mudumbai, R.C., Johnstone, M.A., Wang, R.K., and Chen, P.P. (2016). Optic Disc Perfusion in Primary Open Angle and Normal Tension Glaucoma Eyes Using Optical Coherence Tomography-Based Microangiography. 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