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

Evidence suggests that the cytokine interferon (IFN)-gamma 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-gamma prevents or alleviates GC loss in an experimental desiccating stress (DS) model of dry eye. In this study, we found that topical IFN-gamma 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-gamma produced by pathogenic CD4(+) T cells contributes to DS-induced GC loss, adoptive transfer of CD4(+) T cells isolated from DS exposed donors to naive RAG-1(-/-) recipient mice was performed. Similar to the donor mice, topical IFN-gamma 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-gamma prevents GC loss via modulating apoptosis and maintaining IL-13 signaling. (C) 2013 Elsevier Ltd. All rights reserved.