{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:58:09Z","timestamp":1790272689730,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,11,21]],"date-time":"2007-11-21T00:00:00Z","timestamp":1195603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Pax6<\/jats:italic> is the universal master control gene for eye morphogenesis. Other than retina and lens, Pax6 also expressed in the ocular surface epithelium from early gestation until the postnatal stage, in which little is known about the function of <jats:italic>Pax6<\/jats:italic>. In this study, corneal pannus tissues from patients with ocular surface diseases such as Stevens\u2013Johnson syndrome (SJS), chemical burn, aniridia and recurrent pterygium were investigated. Our results showed that normal ocular surface epithelial cells expressed Pax6. However, corneal pannus epithelial cells from the above patients showed a decline or absence of Pax6 expression, accompanied by a decline or absence of K12 keratin but an increase of K10 keratin and filaggrin expression. Pannus basal epithelial cells maintained nuclear p63 expression and showed activated proliferation, evidenced by positive Ki67 and K16 keratin staining. On 3T3 fibroblast feeder layers, Pax6 immunostaining was negative in clones generated from epithelial cells harvested from corneal pannus from SJS or aniridia, but positive in those from the normal limbal epithelium; whereas western blots showed that some epithelial clones expanded from pannus retained Pax6 expression. Transient transfection of an adenoviral vector carrying <jats:italic>EGFP\u2013Pax6<\/jats:italic> transgenes into these <jats:italic>Pax<\/jats:italic><jats:italic>6<\/jats:italic><jats:sup>\u2212<\/jats:sup> clones increased both Pax6 and K12 keratin expression. These results indicate that <jats:italic>Pax6<\/jats:italic> helps to maintain the normal corneal epithelial phenotype postnatally, and that down\u2010regulation of <jats:italic>Pax6<\/jats:italic> is associated with abnormal epidermal differentiation in severe ocular surface diseases. Reintroduction of activation of the <jats:italic>Pax6<\/jats:italic> gene might be useful in treating squamous metaplasia of the ocular surface epithelium. Copyright \u00a9 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2256","type":"journal-article","created":{"date-parts":[[2007,11,21]],"date-time":"2007-11-21T07:47:39Z","timestamp":1195631259000},"page":"114-122","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Down\u2010regulation of <i>Pax6<\/i> is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases"],"prefix":"10.1002","volume":"214","author":[{"given":"W","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y\u2010T","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Hayashida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Kheirkah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u2010Y","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u2010Y","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SCG","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,11,21]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0294-168"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.5.945"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.161144098"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7914031"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/354522a0"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0493-299"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2173141"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1192-232"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.113.4.1435"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.5.1433"},{"key":"e_1_2_6_12_2","first-page":"1721","article-title":"Characterization of a paired box\u2010 and homeobox\u2010containing quail gene (Pax\u2010QNR) expressed in the neuroretina","volume":"7","author":"Martin P","year":"1992","journal-title":"Oncogene"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(02)00095-7"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-0576"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2005.02.002"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-1118"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.114.3.643"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412458200"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1083"},{"key":"e_1_2_6_20_2","first-page":"2554","article-title":"Identification of the cornea\u2010specific keratin 12 promoter by in vivo particle\u2010mediated gene transfer","volume":"39","author":"Shiraishi A","year":"1998","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1998.0593"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1177\/112067210301300201"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(90)32478-8"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.99.6.2279"},{"key":"e_1_2_6_25_2","first-page":"827","article-title":"The induction of keratinization in the corneal epithelium. 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