April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
The Role of β-catenin Signaling in Ocular Surface Homeostasis and Tumorigenesis
Author Affiliations & Notes
  • C.-Y. Liu
    Ophthalmology, Univ of Cincinnati, Cincinnati, Ohio
  • M. Call
    Ophthalmology, Univ of Cincinnati, Cincinnati, Ohio
  • Y. Zhang
    Ophthalmology, Univ of Cincinnati, Cincinnati, Ohio
  • W. W. Kao
    Ophthalmology, Univ of Cincinnati, Cincinnati, Ohio
  • Footnotes
    Commercial Relationships  C.-Y. Liu, None; M. Call, None; Y. Zhang, None; W.W. Kao, None.
  • Footnotes
    Support  NIH Grant EY10556, EY11845, EY13755, RPB, and Ohio Lion Foundation for Eye Research
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 2594. doi:
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      C.-Y. Liu, M. Call, Y. Zhang, W. W. Kao; The Role of β-catenin Signaling in Ocular Surface Homeostasis and Tumorigenesis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2594.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : β-catenin signaling has been implicated in two major biological processes of embryonic development and tumorigenesis. In this study, we determined the role of β-catenin in corneal epithelial morphogenesis, homeostasis, and tumorigenesis.

Methods: : Conditional gain- and loss-of-function mutations of the β-catenin gene (Ctnnb1) were specifically expressed in differentiated corneal epithelium, respectively, in vivo.

Results: : Dox-treated Krt12rtTA/w;tetO-Cre;Ctnnb1floxedEx3/w triple transgenic mice all exhibited corneal epithelial hyperplasia at different developmental stages from E18.5 to P30. Immunofluorescent staining showed that nuclear localization of β-catenin correlated well with the hyperplastic transformation. These corneal epithelial hyperplastic lesions loss K12 expression, but maintain high level of p63. The basement membrane components i.e., laminins-1 and -β1 are completely down-regulated. Interestingly, members involved in sonic hedgehog signaling Shh, Smo, and Ptc were all dramatically down-regulated. Moreover, X-gal positive cells completely correlated with the hyperplastic transformation and stromal invasion in the cornea of Dox-induced Krt12rtTA/w;tetO-Cre;Ctnnb1floxed Ex3/w;TOPGAL quadruple transgenic mice. On the other hand, loss of β-catenin from the corneal epithelium did not result in significant abnormality, suggesting that β-catenin is dispensable for the maintenance of corneal epithelial homeostasis. However, conditional ablation of β-catenin in Krt12rtTA/rtTA;tetO-FGF-7;tetO-Cre;Ctnnb1f/f mice treated with Dox prevents corneal epithelial hyperplastic transformation.

Conclusions: : Forced expression of dominant stabilizing mutant β-catenin disrupts corneal homeostasis and leads to hyperplastic transformation, whereas ablation of β-catenin protects against FGF-7-induced corneal hyperplasia. These results suggest that regulation of β-catenin signaling plays a pivotal role in the maintenance of normal corneal epithelial homeostasis.

Keywords: cornea: epithelium • development • signal transduction: pharmacology/physiology 

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