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M. K. Call, C.-Y. Liu, W. W. Kao, M. M. Taketo; The Role of β-catenin in Corneal Wound Healing. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6300.
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Corneal wound healing involves a series of events some of which include proliferation and cell migration. β-catenin (Ctnnb1) is a molecule which has dual functions serving as a mediator in the canonical Wnt signaling pathway as well as being a component of adherens complexes and thus has been implicated in both proliferation and cell migration. Based on this information, we set out to determine the role of Ctnnb1 in wound healing following corneal epithelial debridement.
To determine the role of Ctnnb1 in corneal wound healing a 2 mm debridement wound was made in the corneal epithelium in both gain- and loss-of-function mutations of the Ctnnb1 gene, Krt12rtTA/rtTA;tetO-Cre;Ctnnb1floxed Ex3/+ and Krt12rtTA/rtTA;tetO-Cre;Ctnnb1f/f mice, respectively. The rate of wound healing was determined between 0 h and 30 h post-debridement via fluorescein uptake. Mice were injected with BrdU 2 h prior to sacrifice to determine the rate of proliferation. All reported research was conducted in compliance with the ARVO statement for the Use of Animals in Ophthalmic and Vision Research.
In the absence of Ctnnb1, there was a delay in the healing rate 18 h after debridement, but by 30 h both the experimental and control corneas have healed. The gain-of-function model showed the opposite effect with an increase in the rate of wound healing as depicted by the complete healing at 24 h in the doxycycline-induced mice and incomplete healing in the control mice. Phalloidin staining did not reveal any striking distinctions in cell shape between the two mouse lines that could attribute to the differences in epithelial wound healing.
These data implicate a role for Ctnnb1 in corneal epithelial wound healing, however; the mechanism, i.e., proliferation or cell migration, by which this is done has not been fully elucidated.
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