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J Pathol ; 214(1): 114-22, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18027901

ABSTRACT

Pax6 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 Pax6. In this study, corneal pannus tissues from patients with ocular surface diseases such as Stevens-Johnson 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 EGFP-Pax6 transgenes into these Pax6(-) clones increased both Pax6 and K12 keratin expression. These results indicate that Pax6 helps to maintain the normal corneal epithelial phenotype postnatally, and that down-regulation of Pax6 is associated with abnormal epidermal differentiation in severe ocular surface diseases. Reintroduction of activation of the Pax6 gene might be useful in treating squamous metaplasia of the ocular surface epithelium.


Subject(s)
Corneal Diseases/metabolism , Down-Regulation , Epithelium, Corneal/metabolism , Eye Proteins/metabolism , Homeodomain Proteins/metabolism , Paired Box Transcription Factors/metabolism , Repressor Proteins/metabolism , Adolescent , Adult , Aged , Cell Differentiation , Cells, Cultured , Child , Corneal Diseases/pathology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Epithelium, Corneal/pathology , Eye Proteins/genetics , Female , Filaggrin Proteins , Homeodomain Proteins/genetics , Humans , Keratin-12/metabolism , Keratins/metabolism , Male , Metaplasia/metabolism , Middle Aged , PAX6 Transcription Factor , Paired Box Transcription Factors/genetics , Repressor Proteins/genetics , Stem Cells/metabolism , Transfection , Up-Regulation
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