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Callah West, Sonia DaSilva, Lou Sun, Deena Mohamed, Jeffrey Travers, Yang Sun; Stat6 Mediated Blepharitis In An Atopic Dermatitis Model: Th2 Implication In Chronic Inflammation?. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1242.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study is to characterize the eyelid inflammatory lesions found in the Stat6VT mouse, which is a murine model of atopic dermatitis. We hypothesize that the constitutive activation of Stat6 leads to chronic periocular inflammation.
SKH1-HrHr wild type mice and mice that express a constitutively active Stat6 (Stat6VT), V547A/T548A, (N=44, 24 respectively) are examined for the development of blepharitis. Eyelids and periorbital tissue were removed and examined by H&E as well as Western blot analysis with antibodies against IL-4, Interferon γ, and CD3. Lid abnormalities of mutant and wild-type mice were characterized. Real-time PCR analyses for Th1 and Th2 markers were performed on mRNA of both wild type and Stat6VT mice.
Compared to wild-type, Stat6VT transgenic mice exhibited increased frequency of blepharitis and periorbital inflammation (N=44, P<0.05). The Stat6VT transgenic mice demonstrated markedly increased eyelid thickness and elevated T-cell infiltrates (N=5, P<0.05). Kaplan-Meier analysis showed that approximately 90% of the Stat6VT animals developed blepharitis as compared to none of the wild-type sibling controls over a 30-week period (N=44, 24 respectively). Real-time PCR analyses performed on the mRNA from both the wild type and Stat6VT mice showed elevated levels of Th2 cytokines (Il-4, IL-10, and IL-13) and no Th1 cytokine (IFN-γ) expression in the eyelid lesions isolated from the Stat6VT mice (N=3, 4 respectively P<0.05).
We have identified a novel animal model of blepharitis implicating IL-4 and Stat6 signaling in the pathogenesis of chronic eyelid inflammation. The Stat6VT transgenic mouse may be an excellent model system for examining future medical therapeutics for immune-mediated blepharitis.
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