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Dry Eye–Induced Conjunctival Epithelial Squamous Metaplasia Is Modulated by Interferon-γ
Abstract
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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“Dry eye is a common disease of the ocular surface that is associated with corneal surface irregularity and blurred vision [155-158].”
BackgroundThe Pathophysiology of Dry Eye Disease
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Metadata
- Authors
- De Paiva, C. S., Villarreal, A. L., Corrales, R. M., Rahman, H. T., Chang, V. Y., Farley, W. J., Stern, M. E., Niederkorn, J. Y., Li, D.-Q., & Pflugfelder, S. C.
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2007-06-01
- Volume
- 48
- Issue
- 6
- Pages
- 2553
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2049207532
- Cited by
- 320
- References
- 35
- FWCI
- 11.84
- Type
- journal article
- Language
- en
- Open access
- closed
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