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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; Dry Eye–Induced Conjunctival Epithelial Squamous Metaplasia Is Modulated by Interferon-γ. Invest. Ophthalmol. Vis. Sci. 2007;48(6):2553-2560. doi: 10.1167/iovs.07-0069.
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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.
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