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(Investigative Ophthalmology and Visual Science. 2005;46:3239-3246.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-0138
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Role of Interferon-{gamma} in a Mouse Model of Allergic Conjunctivitis

Michael E. Stern,1 Karyn Siemasko,1 Jianping Gao,1 Anh Duong,1 Clay Beauregard,2 Virginia Calder,3 and Jerry Y. Niederkorn2

From 1Allergan, Irvine, California; the 2Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas; and the 3Department of Ophthalmology, University College London, London, United Kingdom.

PURPOSE. To characterize the effect of repeated topical exposure to allergen in a mouse model of allergic conjunctivitis and to determine the role of interferon-{gamma} (IFN-{gamma}) in the pathogenesis of allergic conjunctivitis.

METHODS. Wild-type BALB/c mice and IFN-{gamma} knockout (KO) BALB/c mice were sensitized in the footpad with short ragweed (SRW) allergen and challenged topically for seven consecutive days with SRW allergen. The number of splenic CD4+ Th2 cells was determined by flow cytometry, and the cytokine profile of CD4+ T cells from SRW-sensitized mice was evaluated by ELISA. The role of IFN-{gamma} in allergic conjunctivitis was also examined by timed in vivo neutralization with anti-IFN-{gamma} antibody. Allergic conjunctivitis was evaluated clinically and histopathologically.

RESULTS. Repeated topical challenge with SRW allergen induced allergic conjunctivitis that was characterized by lid edema, chemosis, redness, and tearing. Histopathological analysis revealed a marked conjunctival infiltrate that was predominantly neutrophils and eosinophils. IFN-{gamma} KO mice and normal mice treated with anti-IFN-{gamma} antibody displayed milder clinical symptoms of allergic conjunctivitis and a 70% reduction in the number of eosinophils that infiltrated the conjunctiva. Spleen cells from SRW-sensitized mice contained a large population of cells that expressed the Th2 surface marker T1/ST2 and produced IL-4, -5, and -10 and IFN-{gamma} after stimulation with SRW allergen.

CONCLUSIONS. Repeated topical application of SRW allergen induces a form of murine allergic conjunctivitis that mimics the human counterpart. IFN-{gamma} appears to contribute to the pathogenesis of murine allergic conjunctivitis at the effector phase, but not during the initial sensitization stage.




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A. Matsuda, N. Ebihara, N. Kumagai, K. Fukuda, K. Ebe, K. Hirano, C. Sotozono, M. Tei, K. Hasegawa, M. Shimizu, et al.
Genetic Polymorphisms in the Promoter of the Interferon Gamma Receptor 1 Gene Are Associated with Atopic Cataracts
Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 583 - 589.
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