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Hyun Soo Lee, Takaaki Hattori, Sunil Chauhan, Reza Dana; Expression Of Toll-like Receptor (tlr) 4 In The Experimental Dry Eye Cornea. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3769.
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Toll-like receptors (TLRs) activate innate immunity and modulate the adaptive immune response in several autoimmune disorders by regulating the production of inflammatory cytokines and chemokines. The purpose of this study was to investigate the dynamics of corneal expression of TLR-4 in dry eye disease (DED).
Female 7-8 week old C57BL/6 mice were housed in a controlled desiccating environment chamber to induce DED for 7 days. Expressions of TLR-4 at protein and mRNA level in corneal epithelium and stroma were evaluated by flow cytometry and real-time PCR.
Extracellular and intracellular staining of TLR-4 using flow cytometry showed that most TLR-4 was located intracellularly in epithelial cells of the normal cornea. DED induced a significant increase (55%) in the cell surface expression of TLR-4 in corneal epithelial cells compared to those in the normal cornea (P=0.043). Flow cytometric analysis of stromal cells (CD45) showed 114% increase in the TLR-4 expression in DED compared to normal corneas (P=0.047). Real time PCR analysis showed TLR-4 mRNA expression was increased only in the stroma (P=0.033), but not in the epithelium of DED corneas.
Our data demonstrate increased expression of TLR-4 in DED corneas. In addition, our results suggest that upregulation of TLR-4 expression in DED corneal epithelium may be primarily due to the translocation of cytoplasmic TLR-4 to the cell surface. These changes in the corneal expression of TLR-4 may be associated with DED immunopathogenesis.
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