Role of interferon-γ in a mouse model of allergic conjunctivitis

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-γ (TFN-γ) in the pathogenesis of allergic conjunctivitis. METHODS. Wild-type BALB/c mice and IFN-γ knockout (KO) BALB/c mice were sensitized in the footpad with short rag-weed (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-γ in allergic conjunctivitis was also examined by timed in vivo neutralization with anti-IFN-γ 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-γ KO mice and normal mice treated with anti-IFN-γ 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-γ 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-γ appears to contribute to the pathogenesis of murine allergic conjunctivitis at the effector phase, but not during the initial sensitization stage.