Dry eye-induced conjunctival epithelial squamous metaplasia is modulated by interferon-gamma

Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2553-60. doi: 10.1167/iovs.07-0069.


Purpose: To investigate the role of interferon (IFN)-gamma in the pathogenesis of conjunctival squamous metaplasia in dry eye.

Methods: Experimental dry eye was created by subjecting C57BL/6 and IFN-gamma-knockout mice to desiccating environmental stress for 5 or 10 days. T-cell antigens and IFN-gamma were detected by immunohistochemistry. Goblet cells were counted in periodic acid Schiff (PAS)-stained sections. Expression of small, proline-rich protein (SPRR)-2 was evaluated by confocal microscopy. Tear IFN-gamma was measured by immunobead assay.

Results: Dry eye promoted migration of CD4+ T cells and IFN-gamma+ cells into goblet cell zones of the conjunctiva and increased the concentration of IFN-gamma in tears. This migration was accompanied by progressive goblet cell loss and an increase in SPRR-2 expression in the conjunctival epithelium. A significant inverse correlation was observed between the density of infiltrating CD4+ T cells and goblet cells. Dry eye had no effect on conjunctival goblet cell density in IFN-gamma-knockout mice; however, exogenous administration of IFN-gamma significantly decreased goblet cell density after 5 days.

Conclusions: Conjunctival epithelial response to experimental dryness is related to the degree of CD4+ T-cell infiltration and the level of IFN-gamma production. These findings suggest that IFN-gamma plays a pivotal role in promoting conjunctival squamous metaplasia in dry eye, and they provide insight into the immune pathogenesis of keratoconjunctivitis sicca.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Count
  • Cell Movement / physiology
  • Conjunctiva / pathology*
  • Cornified Envelope Proline-Rich Proteins
  • Dry Eye Syndromes / complications*
  • Dry Eye Syndromes / immunology
  • Fluorescent Antibody Technique, Indirect
  • Goblet Cells / pathology
  • Immunoenzyme Techniques
  • Interferon-gamma / pharmacology
  • Interferon-gamma / physiology*
  • Membrane Proteins / metabolism
  • Metaplasia / etiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Protein Precursors / metabolism
  • Recombinant Proteins
  • Tears / metabolism


  • Cornified Envelope Proline-Rich Proteins
  • Membrane Proteins
  • Protein Precursors
  • Recombinant Proteins
  • SPRR2A protein, human
  • Interferon-gamma