Model of allergic keratoconjunctivitis - Stat6 signaling in chronic inflammation

Abstract

 

Purpose

 

The purpose of this study is to characterize the corneal inflammatory lesions found in the Stat6VT mouse as a model for atopic dermatitis. We hypothesize that the constitutive activation of Stat6 results in corneal neovascularization and pannus formation.

 

Methods

 

SKH1-HrHr wild-type mice and mice which express an integrally active Stat6 (Stat6VT), V547A/T548A, (N=20, 24 respectively) where examined for the development of keratoconjunctivitis. Corneas were removed and examined by H&E and PAS staining. Immunoblot analysis was performed with Interleukin-4, Interferon gamma, and CD3. Steroid treatment with clobetasol was performed on affected lesions.

 

Results

 

Compared to wild-type, Stat6VT transgenic mice exhibited increased frequency of corneal neovascularization (N=24, P<0.05). The Stat6VT transgenic mice demonstrated corneal infiltrate as well as neovascularization (N=5, P<0.05). Real-time PCR analyses performed on the mRNA from both the wild type and Stat6VT mice yielded elevated levels of Th2 cytokines isolated from the Stat6VT mice (N=5,5 respectively P<0.05). We showed that clobetasol treatment slowed the development of periocular and corneal lesions.

 

Conclusions

 

Stat6 signaling may play a role in the pathogenesis of chronic ocular inflammation. IL-4 may mediate corneal inflammation in allergic keratoconjunctivitis.

 

 

Figure 1. Corneal infiltrates in STAT6VT mice. (A) WT and (B) STAT6VT mice cornea were stained by H&E. Scale bar represents 10 microns.

 

Keywords: 474 conjunctiva • 557 inflammation • 480 cornea: basic science