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

Cintia S. De Paiva, Arturo L. Villarreal, Rosa M. Corrales, Hassan T. Rahman, Victor Y. Chang, William J. Farley, Michael E. Stern, Jerry Y. Niederkorn, De Quan Li, Stephen C. Pflugfelder

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250 Scopus citations


PURPOSE. To investigate the role of interferon (IFN)-γ in the pathogenesis of conjunctival squamous metaplasia in dry eye. METHODS. Experimental dry eye was created by subjecting C57BL/6 and IFN-γ-knockout mice to desiccating environmental stress for 5 or 10 days. T-cell antigens and IFN-γ 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-γ was measured by immunobead assay. RESULTS. Dry eye promoted migration of CD4 + T cells and IFN-γ+ cells into goblet cell zones of the conjunctiva and increased the concentration of IFN-γ 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-γ-knockout mice; however, exogenous administration of IFN-γ 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-γ production. These findings suggest that IFN-γ plays a pivotal role in promoting conjunctival squamous metaplasia in dry eye, and they provide insight into the immune pathogenesis of keratoconjunctivitis sicca.

Original languageEnglish (US)
Pages (from-to)2553-2560
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number6
StatePublished - Jun 2007

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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