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Stephen C Pflugfelder, Rosa M Corrales, Quianta L Moore, Eugene Volpe, Koray Gumus, Mahira Zaheer, Cintia S. De Paiva; Markers of Squamous Metaplasia in Tear Dysfunction Correlate with Conjunctival Interferon-gamma Expression. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2003.
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To test the hypothesis that markers of squamous metaplasia are associated with altered expression of T helper (Th) cytokines IFN-γ and IL-13 and their receptors in the conjunctiva of subjects with tear dysfunction and controls.
Impression cytology was performed in the temporal bulbar conjunctiva to measure goblet cell density (GCD) and the nasal bulbar conjunctiva to measure gene expression in 65 subjects, including normal control (n = 13), meibomian gland disease (MGD, n = 17), non-Sjögren aqueous deficiency (non-SS ATD, n = 7), and Sjögren aqueous deficiency (SS ATD, n = 37). Goblet cells were counted in digital images of PAS-stained membranes. Gene expression was evaluated by real-time PCR. Tear meniscus height (TMH) was measured by anterior segment OCT. Fluorescein and lissamine green dye staining evaluated corneal and conjunctival disease, respectively. ANOVA with post-hoc analyses were used for determining between group differences and Pearson coefficients were calculated.
The ATD groups had significantly lower TMH and higher ocular surface dye staining than the control and MGD groups. GCD was lowest and SPRR-1A expression highest in the SS ATD group. IFN-γ expression was significantly higher in both ATD groups and IFN-γR was higher than control in all tear dysfunction groups. Expression of IL-13 and its signaling receptor, IL-13Rα1 was similar in all groups, while the IL-13 decoy receptor, IL-13rα2 was higher in all tear dysfunction groups. The number of IFN-γ mRNA transcripts showed significant correlation with TMH (r = -0.37, P = 0.02), lissamine green staining (r = 0.51, P < 0.001), GCD (r = -0.37, P < 0.04) and SPPR-1A (r = 0.32, P < 0.05).
Expression of IFN-γ and its receptor was higher in aqueous tear deficiency. Markers of conjunctival squamous metaplasia showed significant correlation with level of IFN-γ expression. Based on animal and culture studies, these findings suggest that IFN-γ causes squamous metaplasia by altering differentiation and promoting apoptosis in the conjunctival epithelium.
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