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C. S. De Paiva, S. Chotikavanich, S. Pangelinan, X. Zheng, M. R. Butler, W. J. Farley, M. E. Stern, D.-Q. Li, S. C. Pflugfelder; Desiccating Stress Promotes Th-17 Pattern Response in the Conjunctiva. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5420.
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We have previously demonstrated that C57BL/6 mice develop T cell infiltration of the goblet cell rich area of the conjunctiva after desiccating stress. Our purpose was to investigate the pattern of T cell cytokines and their receptors in the conjunctiva in response to desiccating stress.Materials and
Experimental dry eye was created by subjecting 6-8 week old C57BL/6 mice to desiccating environmental stress for 5 or 10 days. MMP-9 and T helper (Th)-1, 2 and 17 associated cytokines in full thickness biopsies of conjunctiva tissue were evaluated by real time PCR. The presence of IL-17 and IL-23 receptors in the murine ocular surface was evaluated by immunohistochemistry. Th-17 associated cytokine mRNA transcripts in human conjunctival epithelia (4 normals and 4 dry eye patients) obtained by impression cytology were also evaluated by real time PCR.
Desiccating stress induced a significant progressive increase of interleukin (IL)- 6, IL-23, IL-17, IFN-γ, and a significant decrease of IL-12 mRNA transcripts in the conjunctiva. Desiccating stress had no effect on TGF-β2, IL-13, IL-4, and IL-2 mRNA levels. MMP-9 and TGF-β1 transcripts increased after desiccating stress. IL-17 and IL-23 receptor positive cells were occasionally seen in the conjunctival stroma and epithelium in the untreated control group, but they were found to increase in number in the epithelium after 5 and 10 days of desiccating stress. The preliminary results evaluating human conjunctiva demonstrated that dry eye patients had higher levels of IL-6, IL-23, IL-17, TGF-β1 and TGF-β2 mRNA transcripts than normal subjects.
Desiccating stress promotes a Th-17 pattern response in the conjunctiva in murine experimental dry eye and also in human dry eye subjects.
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