{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:36:14Z","timestamp":1788568574376,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union","award":["813440"],"award-info":[{"award-number":["813440"]}]},{"name":"ORBITAL\u2014Ocular Research","award":["813440"],"award-info":[{"award-number":["813440"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Glaucoma is a multifactorial neurodegenerative disease and the second leading cause of blindness. Detection of clinically relevant biomarkers would aid better diagnoses and monitoring during treatment. In glaucoma, the protein composition of aqueous humor (AH) is relevant for the discovery of biomarkers. This study analyzes AH protein concentrations of putative biomarkers in patients with primary open-angle glaucoma (POAG) compared to a control group. Biomarkers were selected from known oxidative-stress and inflammatory pathways. Osteopontin (OPN), matrix metalloproteinase 9 (MMP-9), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and interleukin-10 (IL-10) were measured using the ELISA technique. Thirty-two patients were recruited to the study, including sixteen control and sixteen glaucoma patients. The glaucoma group consisted of patients diagnosed with glaucoma. In both groups, the aqueous humor sample was obtained during cataract surgery. A significant increase in OPN, MMP-9, TNF-alpha, and IL-10 was observed in the POAG aqueous humor, compared to the control group (p &lt; 0.05). Of note, the AH of POAG patients contained 5.6 \u00b1 1.2-fold more OPN compared to that of control patients. Different expression profiles of oxidative stress-related and inflammatory biomarkers were observed between patients with POAG and controls. This confirms the reported involvement of inflammatory and oxidative stress pathways in POAG pathophysiology. In the future, several, targeted AH proteins may be used to generate a potential biomarker expression profile of this disease, aiding diagnoses and disease progression monitoring. This approach highlights the importance of biomarkers in the future. Biomarkers provide a way to measure disease progression and response to treatment. In the future, biomarkers will play a more critical role in the toolkit of ophthalmology healthcare professionals as the field moves towards personalized medicine and precision healthcare.<\/jats:p>","DOI":"10.3390\/life13071455","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:25:21Z","timestamp":1687911921000},"page":"1455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["New Biomarker Combination Related to Oxidative Stress and Inflammation in Primary Open-Angle Glaucoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Azza","family":"Dammak","sequence":"first","affiliation":[{"name":"Ocupharm Group Research, Faculty of Optic and Optometry, Universidad Complutense de Madrid, 28037 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Sanchez Naves","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology Palma de Mallorca, 07012 Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Huete-Toral","sequence":"additional","affiliation":[{"name":"Ocupharm Group Research, Faculty of Optic and Optometry, Universidad Complutense de Madrid, 28037 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0054-1731","authenticated-orcid":false,"given":"Gonzalo","family":"Carracedo","sequence":"additional","affiliation":[{"name":"Ocupharm Group Research, Faculty of Optic and Optometry, Universidad Complutense de Madrid, 28037 Madrid, Spain"},{"name":"Faculty of Optic and Optometry, Department Optometry and Vision, C\/Arcos del Jalon 118, 28032 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"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: A review","volume":"311","author":"Weinreb","year":"2014","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.preteyeres.2013.09.001","article-title":"The vast complexity of primary open angle glaucoma: Disease genes, risks, molecular mechanisms and pathobiology","volume":"37","author":"Janssen","year":"2013","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1136\/bjo.86.2.238","article-title":"The definition and classification of glaucoma in prevalence surveys","volume":"86","author":"Foster","year":"2002","journal-title":"Br. J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1080\/02713683.2019.1608261","article-title":"Detection of Proteins Associated with Extracellular Matrix Regulation in the Aqueous Humour of Patients with Primary Glaucoma","volume":"44","author":"Nikhalashree","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e217","DOI":"10.1016\/j.jfo.2020.05.002","article-title":"The trabecular meshwork: Structure, function and clinical implications. A review of the literature","volume":"43","author":"Buffault","year":"2020","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1444-0938.2002.tb02384.x","article-title":"The mechanism of aqueous humour formation","volume":"85","author":"To","year":"2002","journal-title":"Clin. Exp. Optom."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dammak, A., Huete-Toral, F., Carpena-Torres, C., Martin-Gil, A., Pastrana, C., and Carracedo, G. (2021). From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13091376"},{"key":"ref_8","first-page":"e768","article-title":"Tear and aqueous humour cytokine profile in primary open-angle glaucoma","volume":"98","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1167\/iovs.09-4247","article-title":"Tumor necrosis factor-alpha concentrations in the aqueous humor of patients with glaucoma","volume":"51","author":"Sawada","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2147\/OPTH.S19453","article-title":"Tumor necrosis factor-alpha (TNF-\u03b1) levels in aqueous humor of primary open angle glaucoma","volume":"5","author":"Balaiya","year":"2011","journal-title":"Clin. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"812503","DOI":"10.1155\/2015\/812503","article-title":"Altered Expression Levels of MMP1, MMP9, MMP12, TIMP1, and IL-1\u03b2 as a Risk Factor for the Elevated IOP and Optic Nerve Head Damage in the Primary Open-Angle Glaucoma Patients","volume":"2015","author":"Markiewicz","year":"2015","journal-title":"Biomed Res. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"Bio106","DOI":"10.1167\/iovs.17-21723","article-title":"Functional Activity of Matrix Metalloproteinases 2 and 9 in Tears of Patients with Glaucoma","volume":"58","author":"Sahay","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6443","DOI":"10.1167\/iovs.11-7409","article-title":"Expression profile of the matricellular protein osteopontin in primary open-angle glaucoma and the normal human eye","volume":"52","author":"Chowdhury","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.molmet.2014.03.004","article-title":"Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes","volume":"3","author":"Kahles","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5759","DOI":"10.1167\/iovs.10-5558","article-title":"Changes of osteopontin in the aqueous humor of the DBA2\/J glaucoma model correlated with optic nerve and RGC degenerations","volume":"51","author":"Birke","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","first-page":"612","article-title":"Aqueous humor TGF-\u03b22 levels in patients with open-angle glaucoma: A meta-analysis","volume":"21","author":"Agarwal","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1038\/s41598-021-81048-3","article-title":"Aqueous autotaxin and TGF-\u03b2s are promising diagnostic biomarkers for distinguishing open-angle glaucoma subtypes","volume":"11","author":"Igarashi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/IJG.0b013e318181284f","article-title":"Mitochondrial dysfunction and glaucoma","volume":"18","author":"Kong","year":"2009","journal-title":"J. Glaucoma"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"995","DOI":"10.3892\/ijmm.2016.2714","article-title":"Oxidative stress in the trabecular meshwork (Review)","volume":"38","author":"Zhao","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1167\/iovs.07-1361","article-title":"Mitochondrial complex I defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: Protection by antioxidants","volume":"49","author":"He","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1097\/IJG.0b013e318255bb4a","article-title":"Analysis of normal retinal nerve fiber layer thickness by age, sex, and race using spectral domain optical coherence tomography","volume":"22","author":"Alasil","year":"2013","journal-title":"J. Glaucoma"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.ajo.2008.01.004","article-title":"Anterior chamber depth and chamber angle and their associations with ocular and general parameters: The Beijing Eye Study","volume":"145","author":"Xu","year":"2008","journal-title":"Am. J. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8672","DOI":"10.1167\/iovs.11-7480","article-title":"Prevalence and characteristics of primary angle-closure diseases in a rural adult Chinese population: The Handan Eye Study","volume":"52","author":"Liang","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3109\/02713683.2014.968935","article-title":"Gender difference in the pathophysiology and treatment of glaucoma","volume":"40","author":"Tehrani","year":"2015","journal-title":"Curr. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1014853","DOI":"10.3389\/fendo.2022.1014853","article-title":"Osteopontin\u2014The stirring multifunctional regulatory factor in multisystem aging","volume":"13","author":"Du","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.1167\/iovs.10-5531","article-title":"Proteome analysis of human aqueous humor","volume":"51","author":"Chowdhury","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2460\/ajvr.21.04.0062","article-title":"Evaluation of matrix metalloproteinases and tissue inhibitors of metalloproteinases in aqueous humor of dogs with versus without naturally occurring primary angle-closure glaucoma","volume":"83","author":"Pumphrey","year":"2021","journal-title":"Am. J. Vet. Res."},{"key":"ref_29","first-page":"397","article-title":"The association between matrix metalloprotease-9 gene polymorphisms and primary angle-closure glaucoma in a Chinese Han population","volume":"7","author":"Gao","year":"2014","journal-title":"Int. J. Ophthalmol."},{"key":"ref_30","first-page":"2268","article-title":"MTHFR gene C677T and A1298C polymorphisms and homocysteine levels in primary open angle and primary closed angle glaucoma","volume":"15","author":"Micheal","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1167\/iovs.05-0451","article-title":"IL-1 and TNF induction of matrix metalloproteinase-3 by c-Jun N-terminal kinase in trabecular meshwork","volume":"47","author":"Hosseini","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s00417-006-0440-1","article-title":"Matrix metalloproteinases and their inhibitors in the chamber angle of normal eyes and patients with primary open-angle glaucoma and exfoliation glaucoma","volume":"245","author":"Rekonen","year":"2007","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_33","first-page":"12","article-title":"Investigation of scleral fibronectin in primary open-angle glaucoma: Immunohistochemical study","volume":"125","author":"Zhuravleva","year":"2009","journal-title":"Vestn. Oftalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/ceo.14027","article-title":"Pathogenesis of glaucoma: Extracellular matrix dysfunction in the trabecular meshwork\u2014A review","volume":"50","author":"Keller","year":"2022","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101","DOI":"10.17116\/oftalma2022138041101","article-title":"Primary anterior chamber angle closure: Progression from suspect to glaucoma. Part 1. Frequency and rate of transition from suspected primary angle closure to true angle closure and primary angle closure glaucoma","volume":"138","author":"Kurysheva","year":"2022","journal-title":"Vestn. Oftalmol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/00061198-200402000-00013","article-title":"Increased expression of matrix metalloproteinases in mononuclear blood cells of normal-tension glaucoma patients","volume":"13","author":"Golubnitschaja","year":"2004","journal-title":"J. Glaucoma"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3756","DOI":"10.1167\/iovs.12-9818","article-title":"Association of TP53 polymorphisms with primary open-angle glaucoma: A meta-analysis","volume":"53","author":"Guo","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"146","DOI":"10.17116\/oftalma2020136041146","article-title":"The role of metalloproteinases in the development of primary open-angle glaucoma","volume":"136","author":"Svinareva","year":"2020","journal-title":"Vestn. Oftalmol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chen, X., Chen, Y., Wiggs, J.L., Pasquale, L.R., Sun, X., and Fan, B.J. (2016). Association of Matrix Metalloproteinase-9 (MMP9) Variants with Primary Angle Closure and Primary Angle Closure Glaucoma. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157093"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/eye.2000.141","article-title":"Modulating conjunctival wound healing","volume":"14","author":"Cordeiro","year":"2000","journal-title":"Eye"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1006\/exer.2001.1084","article-title":"Role of transforming growth factor-beta1 and its latent form binding protein in pseudoexfoliation syndrome","volume":"73","author":"Zenkel","year":"2001","journal-title":"Exp. Eye Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"701","DOI":"10.2147\/OPTH.S162999","article-title":"Association of increased levels of plasma tumor necrosis factor alpha with primary open-angle glaucoma","volume":"12","author":"Kondkar","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/aos.13899","article-title":"Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age-related macular degeneration, glaucoma and cataract","volume":"97","author":"Fazil","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jung, Y., Ohn, K., Shin, H., Oh, S.E., Park, C.K., and Park, H.L. (2022). Factors Associated with Elevated Tumor Necrosis Factor-\u03b1 in Aqueous Humor of Patients with Open-Angle Glaucoma. J. Clin. Med., 11.","DOI":"10.3390\/jcm11175232"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"154083","DOI":"10.1016\/j.phymed.2022.154083","article-title":"Gegen Qinlian pills alleviate carrageenan-induced thrombosis in mice model by regulating the HMGB1\/NF-\u03baB\/NLRP3 signaling","volume":"100","author":"Wei","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Rad, F., Dabbagh, A., Dorgalaleh, A., and Biswas, A. (2021). The Relationship between Inflammatory Cytokines and Coagulopathy in Patients with COVID-19. J. Clin. Med., 10.","DOI":"10.3390\/jcm10092020"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"764641","DOI":"10.1155\/2015\/764641","article-title":"Fibrosis Related Inflammatory Mediators: Role of the IL-10 Cytokine Family","volume":"2015","author":"Sziksz","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/2211-5463.12637","article-title":"Comparative analysis of cytokine profiles of glaucomatous tears and aqueous humour reveals potential biomarkers for trabeculectomy complications","volume":"9","author":"Traverso","year":"2019","journal-title":"FEBS Open Bio"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1080\/02713683.2017.1362003","article-title":"Multiplex Cytokine Analysis of Aqueous Humor from the Patients with Chronic Primary Angle Closure Glaucoma","volume":"42","author":"Duvesh","year":"2017","journal-title":"Curr. Eye Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Garweg, J.G., Zandi, S., Pfister, I.B., Skowronska, M., and Gerhardt, C. (2017). Comparison of cytokine profiles in the aqueous humor of eyes with pseudoexfoliation syndrome and glaucoma. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182571"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jtos.2017.03.004","article-title":"Tear cytokine profile of glaucoma patients treated with preservative-free or preserved latanoprost","volume":"15","author":"Urcelay","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.18240\/ijo.2019.10.13","article-title":"Association between interleukin-10 genetic polymorphisms and risk of primary open angle glaucoma in a Chinese Han population: A case-control study","volume":"12","author":"Zhang","year":"2019","journal-title":"Int. J. Ophthalmol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Fakhraie, G., Parvini, F., Ghanavi, J., Saif, S., and Farnia, P. (2020). Association of IL-10 gene promoter polymorphisms with susceptibility to pseudoexfoliation syndrome, pseudoexfoliative and primary open-angle glaucoma. BMC Med. Genet., 21.","DOI":"10.1186\/s12881-020-0969-6"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"942","DOI":"10.2174\/1570159X15666170720094529","article-title":"Modulation of the Immune System for the Treatment of Glaucoma","volume":"16","author":"Bell","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Umeno, A., Yoshida, Y., Kaidzu, S., and Tanito, M. (2022). Positive Association between Aqueous Humor Hydroxylinoleate Levels and Intraocular Pressure. Molecules, 27.","DOI":"10.3390\/molecules27072215"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4851","DOI":"10.1167\/iovs.13-12274","article-title":"Pro-inflammatory cytokines in glaucomatous aqueous and encysted Molteno implant blebs and their relationship to pressure","volume":"54","author":"Freedman","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1167\/iovs.13-13591","article-title":"Inflammation-related cytokines of aqueous humor in acute primary angle-closure eyes","volume":"55","author":"Huang","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1167\/iovs.11-8434","article-title":"Multiplex cytokine analysis of aqueous humor in eyes with primary open-angle glaucoma, exfoliation glaucoma, and cataract","volume":"53","author":"Takai","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1080\/02713683.2018.1449222","article-title":"Matricellular Proteins Play a Potential Role in Acute Primary Angle Closure","volume":"43","author":"Wang","year":"2018","journal-title":"Curr. Eye Res."},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"4075","DOI":"10.2147\/OPTH.S388382","article-title":"A Novel Biomarker in Primary Glaucoma: Aqueous Humor and Serum Levels of Ischemia Modified Albumin (IMA)","volume":"16","author":"Rusmayani","year":"2022","journal-title":"Clin. Ophthalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1080\/14728214.2021.2011858","article-title":"Emerging therapies for dry eye disease","volume":"26","author":"Mason","year":"2021","journal-title":"Expert Opin. Emerg. Drugs"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Roda, M., Corazza, I., Bacchi Reggiani, M.L., Pellegrini, M., Taroni, L., Giannaccare, G., and Versura, P. (2020). Dry Eye Disease and Tear Cytokine Levels\u2014A Meta-Analysis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093111"},{"key":"ref_64","first-page":"1240537","article-title":"Extracellular MMP-9-Based Assessment of Ocular Surface Inflammation in Patients with Primary Open-Angle Glaucoma","volume":"2019","author":"Strzemecka","year":"2019","journal-title":"J. Ophthalmol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1161\/ATVBAHA.118.311577","article-title":"Osteopontin in Vascular Disease","volume":"39","author":"Lok","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Abdelaziz Mohamed, I., Gadeau, A.P., Hasan, A., Abdulrahman, N., and Mraiche, F. (2019). Osteopontin: A Promising Therapeutic Target in Cardiac Fibrosis. Cells, 8.","DOI":"10.3390\/cells8121558"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Lamort, A.S., Giopanou, I., Psallidas, I., and Stathopoulos, G.T. (2019). Osteopontin as a Link between Inflammation and Cancer: The Thorax in the Spotlight. Cells, 8.","DOI":"10.3390\/cells8080815"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/s11883-009-0032-8","article-title":"Osteopontin: A multifunctional protein at the crossroads of inflammation, atherosclerosis, and vascular calcification","volume":"11","author":"Cho","year":"2009","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1097\/BCR.0b013e318240541e","article-title":"Epithelial-mesenchymal transition, TGF-\u03b2, and osteopontin in wound healing and tissue remodeling after injury","volume":"33","author":"Weber","year":"2012","journal-title":"J. Burn Care Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.clinbiochem.2018.07.003","article-title":"The multiple functions and mechanisms of osteopontin","volume":"59","author":"Icer","year":"2018","journal-title":"Clin. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.bbrc.2015.04.081","article-title":"Ovary-dependent emphysema augmentation and osteopontin induction in adult female mice","volume":"461","author":"Niikura","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/gene.2009.15","article-title":"Age- and gender-specific modulation of serum osteopontin and interferon-alpha by osteopontin genotype in systemic lupus erythematosus","volume":"10","author":"Kariuki","year":"2009","journal-title":"Genes Immun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/S0022-5347(05)65925-3","article-title":"The influence of sex hormones on renal osteopontin expression and urinary constituents in experimental urolithiasis","volume":"166","author":"Yagisawa","year":"2001","journal-title":"J. Urol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"El Assar, M., \u00c1lvarez-Bustos, A., Sosa, P., Angulo, J., and Rodr\u00edguez-Ma\u00f1as, L. (2022). Effect of Physical Activity\/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158713"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/7\/1455\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:02:06Z","timestamp":1760126526000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/7\/1455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,27]]},"references-count":74,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["life13071455"],"URL":"https:\/\/doi.org\/10.3390\/life13071455","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,27]]}}}