{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:04:12Z","timestamp":1791911052470,"version":"4.3.4"},"reference-count":113,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T00:00:00Z","timestamp":1551744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Randerson Foundation, UK"}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Anatomical Record"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Keratoconus is the most common ectatic disease of the cornea. The disease is usually detected between ages 15 and 25. Incidence is estimated at one out of every 2000 individuals, with some specific ethnic groups being more at risk. Keratoconus manifests itself as a progressive stromal thinning and deformation of the corneal tissue into a conical shape. The etiology of keratoconus is uncertain, although several studies have associated the disease to environmental factors, behavioral conditions and certain genetic disorders. In an effort to better understand how the corneal stroma becomes compromised, multiple experiments have been conducted over the last few years looking at the cells themselves and the factors they produce. The secretion pathways and levels of inflammatory molecules, growth factors, digestive enzymes, and apoptotic factors are all relevant to keratoconus. This review describes the current knowledge of keratoconic pathological signaling pathways within the cornea that may help future developments in disease prevention, treatment and modeling. Anat Rec, 2019. \u00a9 2019 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ar.24090","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T10:20:13Z","timestamp":1550226013000},"page":"1680-1688","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Keratoconus at a Molecular Level: A Review"],"prefix":"10.1002","volume":"303","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3519-1359","authenticated-orcid":false,"given":"Thomas L. A.","family":"Volatier","sequence":"first","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco C.","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-6531","authenticated-orcid":false,"given":"Che J.","family":"Connon","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,5]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"115","article-title":"TGF\u2010beta and wound healing","volume":"157","author":"Amento EP","year":"1991","journal-title":"Ciba Found Symp"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2017-311495"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2005.074955"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713680903477824"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cxo.12038"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e31823d03e3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2011.05.029"},{"key":"e_1_2_8_9_1","first-page":"425","article-title":"Modification of prostaglandin E2 and collagen synthesis in keratoconus fibroblasts, associated with an increase of interleukin 1 alpha receptor number","volume":"316","author":"Bureau J","year":"1993","journal-title":"C R Acad Sci III"},{"key":"e_1_2_8_10_1","first-page":"63","article-title":"Collagen crosslinking in keratoconus","volume":"17","author":"Cannon DJ","year":"1978","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200981200"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrs.2004.04.072"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(09)00247-4"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-9071.2001.d01-17.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3928\/1081-597X-20030501-09","article-title":"Persistent haze and disorganization of anterior stromal collagen appear unrelated following phototherapeutic keratectomy","volume":"19","author":"Connon CJ","year":"2003","journal-title":"J Refract Surg"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.47.6.321"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2013.278"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-200305000-00008"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2005.09.021"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-7956"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0968"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3928\/0191-3913-19940101-08"},{"issue":"752","key":"e_1_2_8_23_1","first-page":"e2","article-title":"Transforming growth factor\u2010beta signaling pathway activation in Keratoconus","volume":"151","author":"Engler C","year":"2011","journal-title":"Am J Ophthalmol"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0484"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2014.01.017"},{"key":"e_1_2_8_26_1","first-page":"328","article-title":"Recurrent keratoconus in a corneal graft after deep anterior lamellar keratoplasty","volume":"7","author":"Feizi S","year":"2012","journal-title":"J Ophthalmic Vis Res"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ico.0000178743.06340.2c"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.06.010"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2015.63"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/370555a0"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6700652"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2016.12.015"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000000408"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-199303000-00010"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/795738"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.10030"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300048200"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(97)30123-7"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14874"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1243819"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2015.01.023"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-30964-y"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(98)00021-4"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2010.185868"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2011.01.008"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.429"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-016-1283-z"},{"key":"e_1_2_8_48_1","first-page":"1364","article-title":"Effect of PDGF, IL\u20101alpha, and BMP2\/4 on corneal fibroblast chemotaxis: expression of the platelet\u2010derived growth factor system in the cornea","volume":"40","author":"Kim WJ","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1999.0719"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-30372-2"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e31820cd61d"},{"key":"e_1_2_8_52_1","first-page":"2244","article-title":"The three\u2010dimensional organization of collagen fibrils in the human cornea and sclera","volume":"32","author":"Komai Y","year":"1991","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000000012"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3781"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199709)172:3<361::AID-JCP10>3.0.CO;2-9"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2015.07.002"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2008.11.001"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/jfb6020422"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2014.240"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1957.sp005758"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e318030df5a"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0000000000000455"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-15100"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2018.05.019"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.85.4.437"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.31.21491"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0968"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/317068"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.4137\/OED.S17204"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20030810"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb09626.x"},{"key":"e_1_2_8_72_1","first-page":"577","article-title":"Keratoconus in vitro and the key players of the TGF\u2010beta pathway","volume":"21","author":"Priyadarsini S","year":"2015","journal-title":"Mol Vis"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(97)00119-7"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrs.2014.09.033"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103063"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0350849"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00587603"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1234"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clae.2010.04.006"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084067"},{"key":"e_1_2_8_81_1","first-page":"540","article-title":"On the fine structure of the human cornea with special reference to the problem of transparency","volume":"73","author":"Schwarz W","year":"1966","journal-title":"Z Zellforsch Mikrosk Anat"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006324-199711000-00029"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0200704"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-9071.2004.00805.x"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184628"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(01)00015-5"},{"key":"e_1_2_8_87_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1242\/jcs.4.2.421","article-title":"Observations on the collagen and proteinpolysaccharide complex of rabbit cornea stroma","volume":"4","author":"Smith JW","year":"1969","journal-title":"J Cell Sci"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-9071.2010.02228.x"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e3180334f78"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAT.0b013e3283511b42"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(00)00159-7"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1129"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-199501000-00013"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1990.53"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.icl.0000189038.74139.4a"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2017.05.009"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrs.2014.08.045"},{"key":"e_1_2_8_98_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20000828)93:5<403::AID-AJMG11>3.0.CO;2-A"},{"key":"e_1_2_8_99_1","first-page":"1543","article-title":"Hepatocyte growth factor, keratinocyte growth factor, and other growth factor\u2010receptor systems in the lens","volume":"38","author":"Weng J","year":"1997","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_8_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2012.03.018"},{"key":"e_1_2_8_101_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1998.0603"},{"key":"e_1_2_8_102_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1996.0038"},{"key":"e_1_2_8_103_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1994.1152"},{"key":"e_1_2_8_104_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-200007000-00001"},{"key":"e_1_2_8_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(98)00017-2"},{"key":"e_1_2_8_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(02)02220-1"},{"key":"e_1_2_8_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90395-S"},{"key":"e_1_2_8_108_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/852986"},{"key":"e_1_2_8_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2009.08.024"},{"key":"e_1_2_8_110_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.2.163"},{"key":"e_1_2_8_111_1","first-page":"1036","article-title":"Protective effects of the galectin\u20101 protein on in vivo and in vitro models of ocular inflammation","volume":"21","author":"Zanon Cde F","year":"2015","journal-title":"Mol Vis"},{"key":"e_1_2_8_112_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145815"},{"key":"e_1_2_8_113_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e31823f8d3c"},{"key":"e_1_2_8_114_1","doi-asserted-by":"publisher","DOI":"10.3109\/9781420044348"}],"container-title":["The Anatomical Record"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Far.24090","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ar.24090","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ar.24090","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ar.24090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T14:21:30Z","timestamp":1759933290000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/ar.24090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,5]]},"references-count":113,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1002\/ar.24090"],"URL":"https:\/\/doi.org\/10.1002\/ar.24090","archive":["Portico"],"relation":{},"ISSN":["1932-8486","1932-8494"],"issn-type":[{"value":"1932-8486","type":"print"},{"value":"1932-8494","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,5]]},"assertion":[{"value":"2018-06-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}