STAT6-mediated keratitis and blepharitis: a novel murine model of ocular atopic dermatitis.
Atopic dermatitis (AD) is a common inflammatory disease that can affect the eye, resulting in ocular pathologies, including blepharitis, keratitis, and uveitis; however, the pathogenic mechanisms underlying the ocular manifestations of AD are not well understood.



In the present study, we characterized the ocular pathologies that develop in the Stat6VT mouse model of AD. We examined the cytokine profile of the eyelid lesions, measured the behavioral response, and documented the treatment response to topical steroids.



Our results show that Stat6VT mice spontaneously developed blepharitis, keratitis, and uveitis similar to that observed in patients with AD. Histologic findings of allergic inflammation in affected eyelids in this model include the presence of a lymphocyte-predominant infiltrate and tissue eosinophilia in the dermis. Gene expression analysis of affected eyelid tissue by quantitative PCR revealed increased amounts of mRNAs for the Th2 cytokines IL-4, IL-5, and IL-13. In addition, increased eyelid scratching was seen in Stat6VT mice with blepharitis. Topical treatment with the corticosteroid clobetasol reduced eyelid inflammation, tissue eosinophilia, and Th2 cytokine expression.



The development of AD-like ocular pathologies in this model supports the idea that in humans, AD-associated disease of the eye may be driven by Th2-mediated inflammation and demonstrates that the Stat6VT mouse may be a useful system in which to further investigate pathogenesis of and treatment strategies for blepharitis and other ocular diseases that develop in association with AD.
Department of Dermatology, Indiana University, Indianapolis, Indiana, United States Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, Unites States.
Matthew J
MJ
Turner
Department of Dermatology, Indiana University, Indianapolis, Indiana, United States.
Sonia
S
DaSilva-Arnold
Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University, Indianapolis, Indiana, United States.
Na
N
Luo
Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University, Indianapolis, Indiana, United States.
Xinyao
X
Hu
Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University, Indianapolis, Indiana, United States.
Callah C
CC
West
Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University, Indianapolis, Indiana, United States.
Lou
L
Sun
Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University, Indianapolis, Indiana, United States.
Christopher
C
Hill
Department of Pathology, Indiana University, Indianapolis, Indiana, United States.
Joshua
J
Bradish
Department of Pediatrics, Indiana University, Indianapolis, Indiana, United States.
Mark H
MH
Kaplan
Department of Dermatology, Indiana University, Indianapolis, Indiana, United States Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, Unites States.
Jeffrey B
JB
Travers
Department of Dermatology, Indiana University, Indianapolis, Indiana, United States Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University, Indianapolis, Indiana, United States.
Yang
Y
Sun
D000818:Animals; D001762:Blepharitis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015151:Immunoblotting; D007634:Keratitis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D050800:STAT6 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*
D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D012313:RNA
STAT6; atopic blepharitis; ocular atopic dermatitis