Interferon-gamma deficiency protects against aging-related goblet cell loss

Oncotarget. 2016 Oct 4;7(40):64605-64614. doi: 10.18632/oncotarget.11872.


Aging is a well-recognized risk factor for dry eye. Interferon-gamma (IFN-γ) has been implicated in conjunctival keratinization and goblet cell loss in dry eye. We investigated the role of IFN-γ in age-related dry eye by evaluating young (8 weeks) and aged (15 months; 15M) C57BL/6 (B6) and IFN-γKO mice. Age effects on the conjunctiva and cornea epithelium were assessed with PAS staining and corneal staining, respectively. Expression of T cell-related cytokines (IL-17A, IFN-γ), chemokines (CXCL10 and CCL20), in the ocular surface epithelium was evaluated by real time PCR. A significant decrease in filled goblet cells was noted in 15M B6 mice and this was significantly lower than age and sex-matched IFN-γKO mice. Aged male B6 had significantly higher IFN-γ, and CXCL10 mRNA in their conjunctiva than female B6 mice. Aged IFN-γKO females had significantly higher IL-17A mRNA in conjunctiva than IFN-γKO males and B6 mice. Corneal barrier dysfunction was observed in 15M female B6 and aged IFN-γKO mice of both sexes; however it was significantly higher in IFN-γKO compared to B6 mice. While there was a significant increase in IL 17A, and CCL20 in corneas of aged female B6 and IFN-γKO mice compared to males, these changes were more evident in aged female IFN-γKO group.Partial resistance of IFN-γKO mice to aging-induced goblet cell loss indicates IFN-γ is involved in the age-related decline in conjunctival goblet cells. Increased corneal IL-17A expression paralleled corneal barrier disruption in aging female of both strains. IFN-γ appears to suppress IL-17A on the ocular surface.

Keywords: Gerotarget; IL-17; aging; dry eye; goblet cells; interferon-gamma.

MeSH terms

  • Aging / physiology*
  • Animals
  • Cells, Cultured
  • Chemokine CCL20 / metabolism
  • Chemokine CXCL10 / metabolism
  • Conjunctiva / pathology*
  • Cornea / pathology*
  • Disease Models, Animal
  • Dry Eye Syndromes / immunology*
  • Female
  • Goblet Cells / physiology*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes / immunology*


  • CCL20 protein, mouse
  • Chemokine CCL20
  • Chemokine CXCL10
  • Cxcl10 protein, mouse
  • Interleukin-17
  • Interferon-gamma