First Author | De Paiva CS | Year | 2007 |
Journal | Invest Ophthalmol Vis Sci | Volume | 48 |
Issue | 6 | Pages | 2553-60 |
PubMed ID | 17525184 | Mgi Jnum | J:123281 |
Mgi Id | MGI:3717945 | Doi | 10.1167/iovs.07-0069 |
Citation | De Paiva CS, et al. (2007) Dry eye-induced conjunctival epithelial squamous metaplasia is modulated by interferon-gamma. Invest Ophthalmol Vis Sci 48(6):2553-60 |
abstractText | 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. |