{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T13:05:40Z","timestamp":1793106340765,"version":"4.5.0"},"reference-count":32,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"name":"Openshaw Keratoconus Research Fund"},{"DOI":"10.13039\/100005800","name":"Eye Bank Association of America","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005800","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["EY015523"],"award-info":[{"award-number":["EY015523"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["EY11654"],"award-info":[{"award-number":["EY11654"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Illness Counseling Center"},{"DOI":"10.13039\/100002247","name":"National Marfan Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002247","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research to Prevent Blindness, Inc"},{"name":"Wilmer Professors Research Fund"},{"name":"The Johns Hopkins Medical Institutions"}],"content-domain":{"domain":["ajo.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["American Journal of Ophthalmology"],"published-print":{"date-parts":[[2011,5]]},"DOI":"10.1016\/j.ajo.2010.11.008","type":"journal-article","created":{"date-parts":[[2011,2,19]],"date-time":"2011-02-19T04:27:26Z","timestamp":1298089646000},"page":"752-759.e2","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":47,"title":["Transforming Growth Factor-\u03b2 Signaling Pathway Activation in Keratoconus"],"prefix":"10.1016","volume":"151","author":[{"given":"Christoph","family":"Engler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shukti","family":"Chakravarti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson","family":"Doyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles G.","family":"Eberhart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Stark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Kelliher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert S.","family":"Jun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"7","key":"10.1016\/j.ajo.2010.11.008_bib1","first-page":"1117","article-title":"Expression of degradative enzymes and protease inhibitors in corneas with keratoconus","volume":"39","author":"Zhou","year":"1998","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"4","key":"10.1016\/j.ajo.2010.11.008_bib2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S0896-1549(03)00099-3","article-title":"The genetics of keratoconus","volume":"16","author":"Rabinowitz","year":"2003","journal-title":"Ophthalmol Clin North Am"},{"issue":"7","key":"10.1016\/j.ajo.2010.11.008_bib3","first-page":"S720","article-title":"A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results","volume":"24","author":"Wittig-Silva","year":"2008","journal-title":"J Refract Surg"},{"issue":"5","key":"10.1016\/j.ajo.2010.11.008_bib4","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.jcrs.2007.12.039","article-title":"Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results","volume":"34","author":"Raiskup-Wolf","year":"2008","journal-title":"J Cataract Refract Surg"},{"issue":"2","key":"10.1016\/j.ajo.2010.11.008_bib5","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1076\/0271-3683(200008)2121-VFT662","article-title":"Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) and MMP-2 in normal and keratoconus corneas","volume":"21","author":"Collier","year":"2000","journal-title":"Curr Eye Res"},{"issue":"4","key":"10.1016\/j.ajo.2010.11.008_bib6","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1097\/01.ico.0000183537.45393.1f","article-title":"Altered expression of type XIII collagen in keratoconus and scarred human cornea: increased expression in scarred cornea is associated with myofibroblast transformation","volume":"25","author":"Maatta","year":"2006","journal-title":"Cornea"},{"issue":"7","key":"10.1016\/j.ajo.2010.11.008_bib7","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1096\/fj.03-1273rev","article-title":"TGF-beta signaling and the fibrotic response","volume":"18","author":"Leask","year":"2004","journal-title":"FASEB J"},{"issue":"10","key":"10.1016\/j.ajo.2010.11.008_bib8","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.1167\/iovs.04-0343","article-title":"Microarray studies reveal macrophage-like function of stromal keratocytes in the cornea","volume":"45","author":"Chakravarti","year":"2004","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"2","key":"10.1016\/j.ajo.2010.11.008_bib9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/labinvest.3700375","article-title":"TGFbeta pathobiology in the eye","volume":"86","author":"Saika","year":"2006","journal-title":"Lab Invest"},{"issue":"1","key":"10.1016\/j.ajo.2010.11.008_bib10","first-page":"1","article-title":"Transforming growth factor-beta: biology and clinical relevance","volume":"38","author":"Kim","year":"2005","journal-title":"J Biochem Mol Biol"},{"issue":"2","key":"10.1016\/j.ajo.2010.11.008_bib11","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jdermsci.2003.12.006","article-title":"TGF-beta-induced SMAD signaling and gene regulation: consequences for extracellular matrix remodeling and wound healing","volume":"35","author":"Schiller","year":"2004","journal-title":"J Dermatol Sci"},{"issue":"5","key":"10.1016\/j.ajo.2010.11.008_bib12","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.exer.2004.07.008","article-title":"Growth factors in the anterior segment: role in tissue maintenance, wound healing and ocular pathology","volume":"79","author":"Klenkler","year":"2004","journal-title":"Exp Eye Res"},{"issue":"2","key":"10.1016\/j.ajo.2010.11.008_bib13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.preteyeres.2007.12.002","article-title":"Fibrotic disorders in the eye: targets of gene therapy","volume":"27","author":"Saika","year":"2008","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.ajo.2010.11.008_bib14","first-page":"131198","article-title":"Active transforming growth factor-beta2 is increased in the aqueous humor of keratoconus patients","author":"Maier","year":"2007","journal-title":"Mol Vis"},{"issue":"2","key":"10.1016\/j.ajo.2010.11.008_bib15","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1006\/exer.2001.1028","article-title":"Altered expression of growth factors and cytokines in keratoconus, bullous keratopathy and diabetic human corneas","volume":"73","author":"Saghizadeh","year":"2001","journal-title":"Exp Eye Res"},{"issue":"7","key":"10.1016\/j.ajo.2010.11.008_bib16","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/pros.20735","article-title":"Increased spermine oxidase expression in human prostate cancer and prostatic intraepithelial neoplasia tissues","volume":"68","author":"Goodwin","year":"2008","journal-title":"Prostate"},{"issue":"4","key":"10.1016\/j.ajo.2010.11.008_bib17","doi-asserted-by":"crossref","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"},{"issue":"2","key":"10.1016\/j.ajo.2010.11.008_bib18","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/jcb.22277","article-title":"Distribution of TGF-beta isoforms and signaling intermediates in corneal fibrotic wound repair","volume":"108","author":"Huh","year":"2009","journal-title":"J Cell Biochem"},{"issue":"33","key":"10.1016\/j.ajo.2010.11.008_bib19","doi-asserted-by":"crossref","first-page":"20533","DOI":"10.1016\/S0021-9258(17)30535-5","article-title":"Distinct transforming growth factor-beta (TGF-beta) receptor subsets as determinants of cellular responsiveness to three TGF-beta isoforms","volume":"265","author":"Cheifetz","year":"1990","journal-title":"J Biol Chem"},{"issue":"3","key":"10.1016\/j.ajo.2010.11.008_bib20","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1167\/iovs.09-3860","article-title":"Human corneal fibrosis: an in vitro model","volume":"51","author":"Karamichos","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"13","key":"10.1016\/j.ajo.2010.11.008_bib21","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1242\/dev.124.13.2659","article-title":"TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes","volume":"124","author":"Sanford","year":"1997","journal-title":"Development"},{"issue":"2","key":"10.1016\/j.ajo.2010.11.008_bib22","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/S0014-4827(02)00015-0","article-title":"TGF-beta1-mediated fibroblast-myofibroblast terminal differentiation-the role of smad proteins","volume":"282","author":"Evans","year":"2003","journal-title":"Exp Cell Res"},{"issue":"5","key":"10.1016\/j.ajo.2010.11.008_bib23","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1006\/exer.1999.0719","article-title":"Keratocyte apoptosis associated with keratoconus","volume":"69","author":"Kim","year":"1999","journal-title":"Exp Eye Res"},{"issue":"6","key":"10.1016\/j.ajo.2010.11.008_bib24","first-page":"340","article-title":"Is the corneal degradation in keratoconus caused by matrix-metalloproteinases?","volume":"29","author":"Collier","year":"2001","journal-title":"Clin Experiment Ophthalmol"},{"key":"10.1016\/j.ajo.2010.11.008_bib25","first-page":"5518","article-title":"Electron microscope study of the pathology of keratoconus: I","author":"Teng","year":"1963","journal-title":"Am J Ophthalmol"},{"issue":"4","key":"10.1016\/j.ajo.2010.11.008_bib26","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.bbadis.2006.01.010","article-title":"Keratoconus: matrix metalloproteinase-2 activation and TIMP modulation","volume":"1762","author":"Smith","year":"2006","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.ajo.2010.11.008_bib27","first-page":"131285","article-title":"Interleukin-1alpha downregulates extracellular-superoxide dismutase in human corneal keratoconus stromal cells","author":"Olofsson","year":"2007","journal-title":"Mol Vis"},{"issue":"5","key":"10.1016\/j.ajo.2010.11.008_bib28","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1167\/iovs.02-0565","article-title":"Regulation of MMPs and TIMPs by IL-1beta during corneal ulceration and infection","volume":"44","author":"Xue","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"4","key":"10.1016\/j.ajo.2010.11.008_bib29","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.ophtha.2004.11.050","article-title":"Inflammatory molecules in the tears of patients with keratoconus","volume":"112","author":"Lema","year":"2005","journal-title":"Ophthalmology"},{"issue":"6","key":"10.1016\/j.ajo.2010.11.008_bib30","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1136\/bjo.2008.144253","article-title":"Subclinical keratoconus and inflammatory molecules from tears","volume":"93","author":"Lema","year":"2009","journal-title":"Br J Ophthalmol"},{"issue":"Suppl 2","key":"10.1016\/j.ajo.2010.11.008_bib31","first-page":"15","article-title":"The expression of human corneal MMP-2, MMP-9, proMMP-13 and TIMP-1 in bullous keratopathy and keratoconus","volume":"32","author":"Predovic","year":"2008","journal-title":"Coll Antropol"},{"issue":"Suppl 1","key":"10.1016\/j.ajo.2010.11.008_bib32","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1093\/ndt\/16.suppl_1.114","article-title":"Role of transforming growth factor-beta1 in the progression of chronic allograft nephropathy","volume":"16","author":"Campistol","year":"2001","journal-title":"Nephrol Dial Transplant"}],"container-title":["American Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002939410009037?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002939410009037?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T13:01:56Z","timestamp":1757595716000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002939410009037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["S0002939410009037"],"URL":"https:\/\/doi.org\/10.1016\/j.ajo.2010.11.008","relation":{},"ISSN":["0002-9394"],"issn-type":[{"value":"0002-9394","type":"print"}],"subject":[],"published":{"date-parts":[[2011,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Transforming Growth Factor-\u03b2 Signaling Pathway Activation in Keratoconus","name":"articletitle","label":"Article Title"},{"value":"American Journal of Ophthalmology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajo.2010.11.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2011 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}