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

Exp Eye Res. 2014 Jan;118:117-24. doi: 10.1016/j.exer.2013.11.011. Epub 2013 Dec 4.

Abstract

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.

Keywords: FOXA2; GC; IFN-γ; IL-13; KCS; MUC5AC; apoptosis; dry eye; gel forming mucin secreted by goblet cells; goblet cell; interferon gamma, a cytokine produced by natural killer (NK) and CD4(+) T cells; keratoconjunctivitis sicca.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Apoptosis / drug effects*
  • Cell Count
  • Conjunctiva / drug effects
  • Conjunctiva / metabolism
  • Conjunctiva / pathology*
  • Disease Models, Animal
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / metabolism
  • Dry Eye Syndromes / pathology
  • Female
  • Gene Expression Regulation / drug effects
  • Goblet Cells / drug effects
  • Goblet Cells / metabolism
  • Goblet Cells / pathology*
  • Hepatocyte Nuclear Factor 3-beta / biosynthesis
  • Interferon-gamma / administration & dosage*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA / genetics
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction

Substances

  • Foxa2 protein, mouse
  • Hepatocyte Nuclear Factor 3-beta
  • RNA
  • Interferon-gamma