{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:59:46Z","timestamp":1791928786667,"version":"4.3.4"},"reference-count":60,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"4","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2021,4,6]]},"DOI":"10.1167\/iovs.62.4.4","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T12:28:55Z","timestamp":1617712135000},"page":"4","source":"Crossref","is-referenced-by-count":28,"title":["TGF-\u03b22 Promotes Oxidative Stress in Human Trabecular Meshwork Cells by Selectively Enhancing NADPH Oxidase 4 Expression"],"prefix":"10.1167","volume":"62","author":[{"given":"Vidhya R.","family":"Rao","sequence":"first","affiliation":[{"name":"Research Service, Department of Veterans Affairs, Edward Hines Jr. VA Hospital, Hines, IL, United States"},{"name":"Department of Ophthalmology, Loyola University Health Science Division, Maywood, IL, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Evan B.","family":"Stubbs","sequence":"additional","affiliation":[{"name":"Research Service, Department of Veterans Affairs, Edward Hines Jr. VA Hospital, Hines, IL, United States"},{"name":"Department of Ophthalmology, Loyola University Health Science Division, Maywood, IL, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1136\/bjophthalmol-2015-307223","article-title":"Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis","volume":"100","author":"Kapetanakis","year":"2016","journal-title":"Br J Ophthalmol."},{"key":"bib2","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br J Ophthalmol."},{"key":"bib3","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology."},{"key":"bib4","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.optom.2016.02.003","article-title":"Glaucoma history and risk factors","volume":"10","author":"McMonnies","year":"2017","journal-title":"J Optom."},{"key":"bib5","first-page":"1699","article-title":"Current primary open-angle glaucoma treatments and future directions","volume":"6","author":"Beidoe","year":"2012","journal-title":"Clin Ophthalmol (Auckland, NZ)."},{"key":"bib6","first-page":"37","article-title":"[Open angle glaucoma: epidemiology, pathogenesis and prevention]","volume":"97","author":"Izzotti","year":"2006","journal-title":"Recenti Prog Med."},{"key":"bib8","doi-asserted-by":"publisher","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."},{"key":"bib9","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s004170000252","article-title":"Transforming growth factor beta 2 levels in the aqueous humor in different types of glaucoma and the relation to filtering bleb development","volume":"239","author":"Picht","year":"2001","journal-title":"Graefes Arch Clin Exp Ophthalmol."},{"key":"bib10","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1167\/iovs.05-1060","article-title":"TGFbeta2-induced changes in human trabecular meshwork: implications for intraocular pressure","volume":"47","author":"Fleenor","year":"2006","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"bib11","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1167\/iovs.04-0649","article-title":"Transforming growth factor-beta 2 modulated extracellular matrix component expression in cultured human optic nerve head astrocytes","volume":"46","author":"Fuchshofer","year":"2005","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"bib12","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s00441-011-1274-7","article-title":"The role of TGF-beta in the pathogenesis of primary open-angle glaucoma","volume":"347","author":"Fuchshofer","year":"2012","journal-title":"Cell Tissue Res."},{"key":"bib13","first-page":"1745","article-title":"Transforming growth factor-beta2 increases extracellular matrix proteins in optic nerve head cells via activation of the Smad signaling pathway","volume":"17","author":"Zode","year":"2011","journal-title":"Mol Vis."},{"key":"bib14","doi-asserted-by":"publisher","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":"bib15","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1152\/nips.01443.2003","article-title":"Understanding trabecular meshwork physiology: a key to the control of intraocular pressure?","volume":"18","author":"Llobet","year":"2003","journal-title":"Physiology."},{"key":"bib16","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.exer.2008.01.013","article-title":"Extracellular matrix in the trabecular meshwork","volume":"86","author":"Acott","year":"2008","journal-title":"Exp Eye Res."},{"key":"bib17","first-page":"168","article-title":"Recent developments in understanding the pathophysiology of elevated intraocular pressure","volume":"17","author":"Tan","year":"2006","journal-title":"Curr Opin Ophthalmol."},{"key":"bib18","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1016\/j.exer.2009.02.007","article-title":"The trabecular meshwork outflow pathways: structural and functional aspects","volume":"88","author":"Tamm","year":"2009","journal-title":"Exp Eye Res."},{"key":"bib19","doi-asserted-by":"publisher","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."},{"key":"bib20","doi-asserted-by":"publisher","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":"bib21","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/S0002-9394(03)00788-8","article-title":"Oxidative stress markers in aqueous humor of glaucoma patients","volume":"137","author":"Ferreira","year":"2004","journal-title":"Am J Ophthalmol."},{"key":"bib22","doi-asserted-by":"publisher","first-page":"823","DOI":"10.3109\/02713683.2011.556299","article-title":"Evaluation of oxidative stress markers in aqueous humor of primary open angle glaucoma and primary angle closure glaucoma patients","volume":"39","author":"Goyal","year":"2014","journal-title":"Curr Eye Res."},{"key":"bib23","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1167\/tvst.1.1.4","article-title":"Antioxidants protect trabecular meshwork cells from hydrogen peroxide-induced cell death","volume":"1","author":"Ammar","year":"2012","journal-title":"Transl Vis Sci Technol."},{"key":"bib24","first-page":"2515","article-title":"Effects of hydrogen peroxide-induced oxidative damage on outflow facility and washout in pig eyes","volume":"32","author":"Yan","year":"1991","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"bib25","doi-asserted-by":"publisher","first-page":"295","DOI":"10.3109\/02713680903548970","article-title":"Oxidative stress markers in patients with primary open-angle glaucoma","volume":"35","author":"Ghanem","year":"2010","journal-title":"Curr Eye Res."},{"key":"bib26","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.yexmp.2011.01.001","article-title":"Evaluation of oxidative stress markers in pathogenesis of primary open-angle glaucoma","volume":"90","author":"Majsterek","year":"2011","journal-title":"Exp Mol Pathol."},{"key":"bib27","doi-asserted-by":"publisher","first-page":"5251","DOI":"10.1167\/iovs.09-3871","article-title":"Sensitivity of ocular anterior chamber tissues to oxidative damage and its relevance to the pathogenesis of glaucoma","volume":"50","author":"Izzotti","year":"2009","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"bib28","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/S0079-6123(08)01127-8","article-title":"Oxidative stress and glaucoma: injury in the anterior segment of the eye","volume":"173","author":"Sacca","year":"2008","journal-title":"Prog Brain Res."},{"key":"bib29","doi-asserted-by":"publisher","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":"bib30","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.coph.2012.09.008","article-title":"Oxidative stress and mitochondrial dysfunction in glaucoma","volume":"13","author":"Chrysostomou","year":"2013","journal-title":"Curr Opin Pharmacol."},{"key":"bib31","doi-asserted-by":"publisher","first-page":"3613","DOI":"10.1167\/iovs.19-27542","article-title":"Mitochondrial-targeted antioxidants attenuate TGF-beta2 signaling in human trabecular meshwork cells","volume":"60","author":"Rao","year":"2019","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"bib32","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1074\/jbc.M112.431973","article-title":"Mitochondrial reactive oxygen species regulate transforming growth factor-beta signaling","volume":"288","author":"Jain","year":"2013","journal-title":"J Biolog Chem."},{"key":"bib33","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1007\/s12035-012-8249-x","article-title":"Prenylation of Rho G-proteins: a novel mechanism regulating gene expression and protein stability in human trabecular meshwork cells","volume":"46","author":"Stubbs","year":"2012","journal-title":"Molec Neurobiol."},{"key":"bib34","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.exer.2018.03.001","article-title":"Consensus recommendations for trabecular meshwork cell isolation, characterization and culture","volume":"171","author":"Keller","year":"2018","journal-title":"Exp Eye Res."},{"key":"bib35","doi-asserted-by":"publisher","first-page":"e29260","DOI":"10.4161\/sgtp.29260","article-title":"Novel role of Cdc42 and RalA GTPases in TNF-alpha mediated secretion of CCL2","volume":"5","author":"Langert","year":"2014","journal-title":"Small GTPases."},{"key":"bib36","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods."},{"key":"bib37","doi-asserted-by":"crossref","first-page":"1803619","DOI":"10.1155\/2019\/1803619","article-title":"The association of oxidative stress status with open-angle glaucoma and exfoliation glaucoma: a systematic review and meta-analysis","volume":"2019","author":"Tang","year":"2019","journal-title":"J Ophthalmol."},{"key":"bib38","doi-asserted-by":"publisher","first-page":"2948","DOI":"10.4049\/jimmunol.175.5.2948","article-title":"The role of phase II antioxidant enzymes in protecting memory T cells from spontaneous apoptosis in young and old mice","volume":"175","author":"Kim","year":"2005","journal-title":"J Immunol."},{"key":"bib39","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1001\/archopht.120.6.714","article-title":"The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma","volume":"120","author":"Gordon","year":"2002","journal-title":"Arch Ophthalmol."},{"key":"bib40","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1001\/archopht.120.6.701","article-title":"The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma","volume":"120","author":"Kass","year":"2002","journal-title":"Arch Ophthalmol."},{"key":"bib41","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/oxfordjournals.aje.a113626","article-title":"The epidemiology of open-angle glaucoma: a review","volume":"118","author":"Leske","year":"1983","journal-title":"Am J Epidemiol."},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.7150\/ijbs.25996","article-title":"The Nrf2 signaling in retinal ganglion cells under oxidative stress in ocular neurodegenerative diseases","volume":"14","author":"Liu","year":"2018","journal-title":"Int J Biol Sci."},{"key":"bib43","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1001\/archopht.123.4.458","article-title":"Oxidative DNA damage in the human trabecular meshwork: clinical correlation in patients with primary open-angle glaucoma","volume":"123","author":"Sacca","year":"2005","journal-title":"Arch Ophthalmol."},{"key":"bib44","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of nrf2 in oxidative stress and toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu Rev Pharmacol Toxicol."},{"key":"bib45","doi-asserted-by":"publisher","first-page":"2478","DOI":"10.1016\/j.biocel.2005.05.013","article-title":"Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism","volume":"37","author":"Jezek","year":"2005","journal-title":"Int J Biochem Cell Biol."},{"key":"bib46","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/j.bbadis.2011.12.001","article-title":"Role of peroxisomes in ROS\/RNS-metabolism: implications for human disease","volume":"1822","author":"Fransen","year":"2012","journal-title":"Biochim Biophys Acta."},{"key":"bib47","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1080\/152165400410281","article-title":"Mitochondrial oxidative stress plays a key role in aging and apoptosis","volume":"49","author":"Sastre","year":"2000","journal-title":"IUBMB Life."},{"key":"bib48","doi-asserted-by":"publisher","first-page":"2533","DOI":"10.1167\/iovs.05-1639","article-title":"Mitochondrial abnormalities in patients with primary open-angle glaucoma","volume":"47","author":"Abu-Amero","year":"2006","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"bib49","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.optom.2016.09.003","article-title":"A review of mitochondrial optic neuropathies: from inherited to acquired forms","volume":"10","author":"Pilz","year":"2017","journal-title":"J Optom."},{"key":"bib50","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1097\/ICU.0b013e328349419d","article-title":"Mitochondrial disorders and the eye","volume":"22","author":"Schrier","year":"2011","journal-title":"Curr Opin Ophthalmol."},{"key":"bib51","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1159\/000083019","article-title":"Concentration of transforming growth factor beta2 in aqueous humor","volume":"37","author":"Yamamoto","year":"2005","journal-title":"Ophthalmic Res."},{"key":"bib52","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.exer.2015.12.010","article-title":"Rho GTPase signaling promotes constitutive expression and release of TGF-beta2 by human trabecular meshwork cells","volume":"146","author":"Pervan","year":"2016","journal-title":"Exp Eye Res."},{"key":"bib53","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.redox.2015.09.009","article-title":"Reciprocal regulation of TGF-beta and reactive oxygen species: a perverse cycle for fibrosis","volume":"6","author":"Liu","year":"2015","journal-title":"Redox Biol."},{"key":"bib54","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.redox.2015.08.015","article-title":"Redox-fibrosis: Impact of TGFbeta1 on ROS generators, mediators and functional consequences","volume":"6","author":"Richter","year":"2015","journal-title":"Redox Biol."},{"key":"bib55","doi-asserted-by":"publisher","first-page":"3421","DOI":"10.1167\/iovs.61.2.46","article-title":"TGF-\u00df2 selectively increases NADPH oxidase type 4 (NOX4) expression in human trabecular meshwork (TM) cells","volume":"61","author":"Rao","year":"2020","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"bib56","first-page":"3800","article-title":"TGF-\u00df induces NOX4 and fibrotic genes in trabecular meshwork cells: role in glaucoma","volume":"60","author":"RK G","year":"2019","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"bib57","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.1007\/s00018-012-1010-9","article-title":"The NOX toolbox: validating the role of NADPH oxidases in physiology and disease","volume":"69","author":"Altenhofer","year":"2012","journal-title":"Cell Mol Life Sci."},{"key":"bib58","doi-asserted-by":"publisher","first-page":"e137127","DOI":"10.1172\/jci.insight.137127","article-title":"Brd4-p300 inhibition downregulates Nox4 and accelerates lung fibrosis resolution in aged mice","volume":"5(14)","author":"Sanders","year":"2020","journal-title":"JCI Insight."},{"key":"bib59","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.gene.2014.02.026","article-title":"A far-upstream AP-1\/Smad binding box regulates human NOX4 promoter activation by transforming growth factor-beta","volume":"540","author":"Bai","year":"2014","journal-title":"Gene."},{"key":"bib60","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.4049\/jimmunol.165.4.2190","article-title":"Requirement of hydrogen peroxide generation in TGF-beta 1 signal transduction in human lung fibroblast cells: involvement of hydrogen peroxide and Ca2+ in TGF-beta 1-induced IL-6 expression","volume":"165","author":"Junn","year":"2000","journal-title":"J Immunol."},{"key":"bib7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000458482","article-title":"Achievements and limits of current medical therapy of glaucoma","volume-title":"Glaucoma Surgery.","author":"Kalouda","year":"2017"}],"container-title":["Investigative Opthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2772456","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:28Z","timestamp":1791927088000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2772456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,6]]},"references-count":60,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.62.4.4","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2021,4,6]]}}}