Topical interferon-gamma neutralization prevents conjunctival goblet cell loss in experimental murine dry eye

• Interferon gamma (IFN-γ) inhibits goblet cell differentiation.
• IFN-γ stimulates apoptosis and inhibits IL-13 signaling in the conjunctival epithelium.
• Topically applied anti-IFN-γ inhibits apoptosis and maintains IL-13 signaling.

Evidence suggests that the cytokine interferon (IFN)-γ released by natural killer and CD4+ T cells contributes to the conjunctival goblet cell (GC) loss in dry eye. The purpose of this study was to investigate if topical neutralization of IFN-γ prevents or alleviates GC loss in an experimental desiccating stress (DS) model of dry eye. In this study, we found that topical IFN-γ neutralization significantly decreased DS-induced conjunctival GC loss. This was accompanied by decreased epithelial apoptosis, and increased IL-13 and decreased FoxA2 expression in the forniceal conjunctiva. To establish that IFN-γ produced by pathogenic CD4+ T cells contributes to DS-induced GC loss, adoptive transfer of CD4+ T cells isolated from DS exposed donors to naïve RAG-1−/− recipient mice was performed. Similar to the donor mice, topical IFN-γ neutralization decreased conjunctival GC loss, suppressed apoptosis and increased IL-13 expression in adoptive transfer recipients. In summary, this study demonstrated that topical neutralization of IFN-γ prevents GC loss via modulating apoptosis and maintaining IL-13 signaling.