{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:40:19Z","timestamp":1791690019229,"version":"4.3.4"},"reference-count":41,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2015,5,21]],"date-time":"2015-05-21T00:00:00Z","timestamp":1432166400000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01 EY012712"],"award-info":[{"award-number":["R01 EY012712"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,11,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fuchs\u2019 endothelial corneal dystrophy (FECD) is a major corneal disorder affecting the innermost part of the cornea, leading to visual impairment. As the morphological changes in FECD are mainly observed in the extracellular matrix of the Descemet\u2019s membrane\/endothelial layer, we determined the protein profiles of diseased and control tissues using two relative quantitation MS methods. The first quantitation method, based on the areas of the extracted ion chromatograms, quantified the 51 and 48 most abundant proteins of the Descemet\u2019s membrane\/endothelial layer in patient and control tissues, respectively, of which 10 were significantly regulated. The results indicated that the level of type VIII collagen was unaltered even though the protein previously has been shown to be implicated in familial early-onset forms of the disease. Using the second relative quantitation method, iTRAQ, we identified 22 differentially regulated proteins, many of which are extracellular proteins known to be involved in proper assembly of the basement membrane in other tissues. In total, 26 differentially regulated proteins were identified, of which 6 proteins were regulated in both methods. These results support that the morphological changes observed in FECD are caused in part by an aberrant assembly of the extracellular matrix within the Descemet\u2019s membrane\/endothelial layer.<\/jats:p>","DOI":"10.1021\/pr500252r","type":"journal-article","created":{"date-parts":[[2014,5,21]],"date-time":"2014-05-21T05:51:36Z","timestamp":1400651496000},"page":"4659-4667","source":"Crossref","is-referenced-by-count":45,"title":["Proteomics of Fuchs\u2019\nEndothelial Corneal Dystrophy\nSupport That the Extracellular Matrix of Descemet\u2019s Membrane\nIs Disordered"],"prefix":"10.1021","volume":"13","author":[{"given":"Ebbe Toftgaard","family":"Poulsen","sequence":"first","affiliation":[{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]},{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Dyrlund","sequence":"additional","affiliation":[{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper","family":"Runager","sequence":"additional","affiliation":[{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]},{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Scavenius","sequence":"additional","affiliation":[{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toke Peter","family":"Krogager","sequence":"additional","affiliation":[{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"H\u00f8jrup","sequence":"additional","affiliation":[{"name":"University of Southern Denmark , , ,","place":["Odense, Denmark, 5000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida B.","family":"Th\u00f8gersen","sequence":"additional","affiliation":[{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian W.","family":"Sanggaard","sequence":"additional","affiliation":[{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]},{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Vorum","sequence":"additional","affiliation":[{"name":"Aalborg University Hospital , , ,","place":["Aalborg, Denmark, 9000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Hjortdal","sequence":"additional","affiliation":[{"name":"Aarhus University Hospital , , ,","place":["Aarhus, Denmark, 8000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan J.","family":"Enghild","sequence":"additional","affiliation":[{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]},{"name":"Aarhus University , , ,","place":["Aarhus, Denmark, 8000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,5,21]]},"reference":[{"key":"2026090406143402000_cit1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1750-1172-4-7","article-title":"Corneal\ndystrophies","volume":"4","author":"Klintworth","year":"2009","journal-title":"Orphanet J. Rare Dis."},{"key":"2026090406143402000_cit2","doi-asserted-by":"crossref","first-page":"6959","DOI":"10.1167\/iovs.11-7771","article-title":"Prevalence\nof corneal dystrophies in the United States: estimates from claims\ndata","volume":"52","author":"Musch","year":"2011","journal-title":"Invest. Ophthalmol. Visual Sci."},{"key":"2026090406143402000_cit3","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/01.ico.0000148288.53323.b2","article-title":"A morphologic study of Fuchs dystrophy\nand bullous keratopathy","volume":"24","author":"Yuen","year":"2005","journal-title":"Cornea"},{"key":"2026090406143402000_cit4","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1093\/hmg\/10.21.2415","article-title":"Missense\nmutations in\nCOL8A2, the gene encoding the alpha2 chain of type VIII collagen,\ncause two forms of corneal endothelial dystrophy","volume":"10","author":"Biswas","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"2026090406143402000_cit5","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1167\/iovs.04-0937","article-title":"Inheritance of a novel COL8A2 mutation defines a distinct\nearly-onset subtype of fuchs corneal dystrophy","volume":"46","author":"Gottsch","year":"2005","journal-title":"Invest. Ophthalmol. Visual Sci."},{"key":"2026090406143402000_cit6","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1001\/archopht.1978.03910060424004","article-title":"Corneal endothelial\ndystrophy. A study of 64 families","volume":"96","author":"Krachmer","year":"1978","journal-title":"Arch. Ophthalmol."},{"key":"2026090406143402000_cit7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ajhg.2009.12.001","article-title":"Missense mutations in TCF8 cause late-onset\nFuchs corneal dystrophy and interact with FCD4 on chromosome 9p","volume":"86","author":"Riazuddin","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"2026090406143402000_cit8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1167\/iovs.05-0578","article-title":"Linkage of late-onset\nFuchs corneal dystrophy to a novel locus at 13pTel-13q12.13","volume":"47","author":"Sundin","year":"2006","journal-title":"Invest. Ophthalmol. Visual Sci."},{"key":"2026090406143402000_cit9","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.1167\/iovs.05-1619","article-title":"A common locus for late-onset Fuchs\ncorneal dystrophy\nmaps to 18q21.2-q21.32","volume":"47","author":"Sundin","year":"2006","journal-title":"Invest. Ophthalmol.\nVisual Sci."},{"key":"2026090406143402000_cit10","doi-asserted-by":"crossref","first-page":"5667","DOI":"10.1167\/iovs.09-3764","article-title":"Linkage of a mild late-onset phenotype\nof Fuchs corneal dystrophy to a novel locus at 5q33.1-q35.2","volume":"50","author":"Riazuddin","year":"2009","journal-title":"Invest. Ophthalmol. Visual Sci."},{"key":"2026090406143402000_cit11","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1056\/NEJMoa1007064","article-title":"E2-2 protein and Fuchs\u2019s\ncorneal dystrophy","volume":"363","author":"Baratz","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"2026090406143402000_cit12","doi-asserted-by":"crossref","first-page":"e46742","DOI":"10.1371\/journal.pone.0046742","article-title":"Differing roles for\nTCF4 and COL8A2 in central corneal thickness and Fuchs endothelial\ncorneal dystrophy","volume":"7","author":"Igo","year":"2012","journal-title":"PLoS One"},{"key":"2026090406143402000_cit13","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1093\/hmg\/ddm337","article-title":"SLC4A11 mutations in Fuchs endothelial corneal\ndystrophy","volume":"17","author":"Vithana","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"2026090406143402000_cit14","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1167\/iovs.07-1529","article-title":"Decreased expression\nof peroxiredoxins\nin Fuchs\u2019 endothelial dystrophy","volume":"49","author":"Jurkunas","year":"2008","journal-title":"Invest.\nOphthalmol. Visual Sci."},{"key":"2026090406143402000_cit15","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.2353\/ajpath.2010.100279","article-title":"Evidence of oxidative\nstress in the pathogenesis of fuchs endothelial corneal dystrophy","volume":"177","author":"Jurkunas","year":"2010","journal-title":"Am. J. Pathol."},{"key":"2026090406143402000_cit16","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1167\/iovs.02-0268","article-title":"Expression and function of receptors for advanced glycation\nend products in bovine corneal endothelial cells","volume":"44","author":"Kaji","year":"2003","journal-title":"Invest. Ophthalmol. Visual Sci."},{"key":"2026090406143402000_cit17","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.ophtha.2006.10.049","article-title":"Advanced glycation end products and receptors in Fuchs\u2019\ndystrophy corneas undergoing Descemet\u2019s stripping with endothelial\nkeratoplasty","volume":"114","author":"Wang","year":"2007","journal-title":"Ophthalmology"},{"key":"2026090406143402000_cit18","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3109\/02713689609017610","article-title":"The composition of wide-spaced collagen in normal and\ndiseased Descemet\u2019s membrane","volume":"15","author":"Levy","year":"1996","journal-title":"Curr. Eye\nRes."},{"key":"2026090406143402000_cit19","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1542-0124(12)70232-X","article-title":"Fuchs endothelial\ncorneal dystrophy","volume":"8","author":"Elhalis","year":"2010","journal-title":"Ocul. Surf."},{"key":"2026090406143402000_cit20","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1167\/iovs.08-2525","article-title":"Colocalization\nof increased transforming\ngrowth factor-induced protein (TGFBIp) and clusterin in Fuchs endothelial\ncorneal dystrophy","volume":"50","author":"Jurkunas","year":"2008","journal-title":"Invest. Ophthalmol. Visual\nSci."},{"key":"2026090406143402000_cit21","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1038\/ejhg.2011.248","article-title":"Association\nof TCF4 and CLU polymorphisms with Fuchs\u2019 endothelial dystrophy\nand implication of CLU and TGFBI proteins in the disease process","volume":"20","author":"Kuot","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"2026090406143402000_cit22","doi-asserted-by":"crossref","first-page":"4231","DOI":"10.1021\/pr300358k","article-title":"Human cornea proteome:\nidentification and quantitation of the proteins of the three main\nlayers including epithelium, stroma, and endothelium","volume":"11","author":"Dyrlund","year":"2012","journal-title":"J. Proteome Res."},{"key":"2026090406143402000_cit23","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1093\/bioinformatics\/btq054","article-title":"Skyline: an open source document editor for creating\nand analyzing targeted proteomics experiments","volume":"26","author":"MacLean","year":"2010","journal-title":"Bioinformatics"},{"key":"2026090406143402000_cit24","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1002\/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2","article-title":"Probability-based\nprotein identification by searching sequence databases using mass\nspectrometry data","volume":"20","author":"Perkins","year":"1999","journal-title":"Electrophoresis"},{"key":"2026090406143402000_cit25","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1074\/mcp.M500230-MCP200","article-title":"Absolute\nquantification of proteins by LCMSE: a virtue of parallel MS acquisition","volume":"5","author":"Silva","year":"2006","journal-title":"Mol. Cell Proteomics"},{"key":"2026090406143402000_cit26","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1002\/pmic.201200109","article-title":"MS Data Miner: a web-based software tool to analyze,\ncompare, and share mass spectrometry protein identifications","volume":"12","author":"Dyrlund","year":"2012","journal-title":"Proteomics"},{"key":"2026090406143402000_cit27","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.1167\/iovs.05-0497","article-title":"Fuchs corneal dystrophy: aberrant collagen distribution\nin an L450W mutant of the COL8A2 gene","volume":"46","author":"Gottsch","year":"2005","journal-title":"Invest.\nOphthalmol. Visual Sci."},{"key":"2026090406143402000_cit28","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0065-230X(09)04006-8","article-title":"Chapter 6:\nThe chaperone action of Clusterin and its putative role in quality\ncontrol of extracellular protein folding","volume":"104","author":"Wyatt","year":"2009","journal-title":"Adv.\nCancer Res."},{"key":"2026090406143402000_cit29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.4161\/cam.21831","article-title":"Laminins\nin basement membrane assembly","volume":"7","author":"Hohenester","year":"2013","journal-title":"Cell Adhes. Migr."},{"key":"2026090406143402000_cit30","doi-asserted-by":"crossref","first-page":"26522","DOI":"10.1074\/jbc.272.42.26522","article-title":"Type VI\ncollagen anchors endothelial basement membranes by interacting with\ntype IV collagen","volume":"272","author":"Kuo","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2026090406143402000_cit31","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.matbio.2011.03.002","article-title":"Collagen\nVI is a basement membrane component that regulates\nepithelial cell-fibronectin interactions","volume":"30","author":"Groulx","year":"2011","journal-title":"Matrix\nBiol."},{"key":"2026090406143402000_cit32","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.biocel.2010.12.010","article-title":"The matrilins:\nmodulators of extracellular matrix assembly","volume":"43","author":"Klatt","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2026090406143402000_cit33","doi-asserted-by":"crossref","first-page":"22163","DOI":"10.1074\/jbc.M610994200","article-title":"Abnormal collagen fibrils in cartilage of matrilin-1\/matrilin-3-deficient\nmice","volume":"282","author":"Nicolae","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2026090406143402000_cit34","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1002\/humu.21182","article-title":"A matrilin-3 mutation\nassociated with osteoarthritis\ndoes not affect collagen affinity but promotes the formation of wider\ncartilage collagen fibrils","volume":"31","author":"Otten","year":"2010","journal-title":"Hum. Mutat."},{"key":"2026090406143402000_cit35","doi-asserted-by":"crossref","first-page":"5250","DOI":"10.1016\/S0021-9258(18)42759-7","article-title":"Binding of the proteoglycan\ndecorin to collagen type VI","volume":"267","author":"Bidanset","year":"1992","journal-title":"J. Biol. Chem."},{"key":"2026090406143402000_cit36","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0945-053X(96)90137-7","article-title":"Characterization\nof the interactions of type XII collagen with two small proteoglycans\nfrom fetal bovine tendon, decorin and fibromodulin","volume":"15","author":"Font","year":"1996","journal-title":"Matrix Biol."},{"key":"2026090406143402000_cit37","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1021\/bi400212m","article-title":"The insoluble TGFBIp\nfraction of the cornea is covalently linked via a disulfide bond to\ntype XII collagen","volume":"52","author":"Runager","year":"2013","journal-title":"Biochemistry"},{"key":"2026090406143402000_cit38","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1111\/febs.12136","article-title":"The regulatory roles\nof small leucine-rich proteoglycans\nin extracellular matrix assembly","volume":"280","author":"Chen","year":"2013","journal-title":"FEBS J."},{"key":"2026090406143402000_cit39","doi-asserted-by":"crossref","first-page":"21672","DOI":"10.1074\/jbc.M301169200","article-title":"Keratocan-deficient\nmice display alterations in corneal structure","volume":"278","author":"Liu","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2026090406143402000_cit40","first-page":"562","article-title":"Candidate\ngene study to investigate the genetic determinants of normal variation\nin central corneal thickness","volume":"16","author":"Dimasi","year":"2010","journal-title":"Mol. Vis."},{"key":"2026090406143402000_cit41","doi-asserted-by":"crossref","first-page":"D1063","DOI":"10.1093\/nar\/gks1262","article-title":"The PRoteomics IDEntifications\n(PRIDE) database and associated tools: status in 2013","volume":"41","author":"Vizcai\u0301no","year":"2013","journal-title":"Nucleic Acids Res."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/pr500252r","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/13\/11\/4659\/13544226\/pr500252r.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/13\/11\/4659\/13544226\/pr500252r.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:33:52Z","timestamp":1788518032000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/13\/11\/4659\/1339646\/Proteomics-of-Fuchs-Endothelial-Corneal-Dystrophy"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,21]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,5,21]]},"published-print":{"date-parts":[[2014,11,7]]}},"URL":"https:\/\/doi.org\/10.1021\/pr500252r","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,21]]}}}