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(Investigative Ophthalmology and Visual Science. 2007;48:2553-2560.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-0069
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Dry Eye–Induced Conjunctival Epithelial Squamous Metaplasia Is Modulated by Interferon-{gamma}

Cintia S. De Paiva,1 Arturo L. Villarreal,1 Rosa M. Corrales,1 Hassan T. Rahman,1 Victor Y. Chang,1 William J. Farley,1 Michael E. Stern,2 Jerry Y. Niederkorn,3 De-Quan Li,1 and Stephen C. Pflugfelder1

1From the Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas; 2Allergan Inc., Irvine, California; and the 3Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas.

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.




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