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JM Sivak, ME Fini; Pax-6 Deficient Mice Show Altered Phenotype and Gene Expression During Corneal Re-Epithelialization . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4197.
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Purpose: Pax-6 is a transcription factor that directs important events during eye formation. It is also expressed in the adult eye, however, it’s role in adults is unclear. Previously we reported that Pax-6 protein is increased in corneal epithelium migrating to repair a wound, and controls transcriptional promoter activity of the gene for the matrix metalloproteinase gelatinase B (gelB) (Dev. Biol. 222:41-54). GelB is expressed at the migrating wound edge and its loss was recently reported to cause defects in corneal wound healing (Mohan et al, J. Biol. Chem, 277: in press). We hypothesized that a reduction in Pax-6 activity should consequently reduce the expression of gelB and create a similar wound phenotype. The current study investigates the role of Pax-6 during corneal wound healing in vivo using mice with a heterozygous deletion of the Pax-6 gene (Sey). Methods: The corneal epithelium was debrided on wild-type and heterozygous Sey mice and allowed to heal for eight hours. The mice were then sacrificed and their eyes sectioned and stained using antibodies to gelB and the inflammatory cell marker, Mac-1. Although heterozygous Sey eyes are microopthalmic, care was taken that the wounds in both wild-type and Sey mice were the same 1mm diameter. Results: Wounded Sey corneas showed little or no increase in gelB expression at the wound edge, contrasting with the normal increase observed in wounded wild type corneas. Also Sey wounds showed a clear increase in inflammatory cell infiltration as compared with wild types. Unwounded Sey corneas showed no signs of inflammation or of altered gelB expression. Also, an increased rate of re-epithelialization appeared to occur in Sey eyes compared to wild types. Conclusions: These experiments indicate that reduction of Pax-6 activity leads to a loss of gel B expression in vivo, along with increased inflammation and re-epithelialization rate. These differences in corneal wound healing in Sey mice are consistent with those observed recently in gelB knockout mice, and suggest an active role for Pax-6 in maintenance and repair of the adult cornea.
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