{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:51:35Z","timestamp":1780512695298,"version":"3.54.1"},"reference-count":34,"publisher":"BMJ","issue":"3","funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["K08EY027474"],"award-info":[{"award-number":["K08EY027474"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ellen A. 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Collagen type XII (<jats:italic>COL12A1<\/jats:italic>), which localises to Bowman\u2019s layer (BL), is thought to function in stress-bearing areas, such as BL. Given the putative protective role of<jats:italic>COL12A1<\/jats:italic>in biomechanical stability, this study aims to characterise<jats:italic>COL12A1<\/jats:italic>expression in all corneal layers involved in KC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>TaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally,<jats:italic>COL12A1<\/jats:italic>was knocked out in vitro in immortalised HEK293 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>COL12A1<\/jats:italic>expression was reduced at transcript levels in KC epithelium compared with controls (ratio: 0.58, p&lt;0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane and stroma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The apparent absence of COL12A1 in KC BL, together with the functional importance that<jats:italic>COL12A1<\/jats:italic>is thought to have in stress bearing areas, suggests that<jats:italic>COL12A1<\/jats:italic>may play a role in the pathogenesis of KC. Further studies are necessary to investigate the mechanisms that lead to<jats:italic>COL12A1<\/jats:italic>dysregulation in KC.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bjo-2022-322180","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T18:21:08Z","timestamp":1675707668000},"page":"343-348","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Collagen type XII is undetectable in keratoconus Bowman\u2019s layer"],"prefix":"10.1136","volume":"108","author":[{"given":"Mohammed","family":"Rigi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1065-4035","authenticated-orcid":false,"given":"Hyeck-Soo","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0216-9443","authenticated-orcid":false,"given":"Loren","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Matthaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2366-235X","authenticated-orcid":false,"given":"Divya","family":"Srikumaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert S","family":"Jun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles G","family":"Eberhart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1678-6437","authenticated-orcid":false,"given":"Uri S","family":"Soiberman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"2024022109050582000_108.3.343.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2017.06.009"},{"key":"2024022109050582000_108.3.343.2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ajo.2016.12.015","article-title":"Age-specific incidence and prevalence of keratoconus: a nationwide registration study","volume":"175","author":"Godefrooij","year":"2017","journal-title":"Am J Ophthalmol"},{"key":"2024022109050582000_108.3.343.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.micron.2012.02.014"},{"key":"2024022109050582000_108.3.343.4","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/ICU.0000000000000570","article-title":"Update on Bowman layer transplantation","volume":"30","author":"Tong","year":"2019","journal-title":"Curr Opin Ophthalmol"},{"key":"2024022109050582000_108.3.343.5","doi-asserted-by":"publisher","DOI":"10.1097\/PAT.0b013e3283511b42"},{"key":"2024022109050582000_108.3.343.6","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.116.1.62"},{"key":"2024022109050582000_108.3.343.7","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/BF00170550","article-title":"Immunogold fine structural localization of extracellular matrix components in aged human cornea. 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