Dry eye disease (DED) is an inflammatory disorder of the ocular surface seriously affecting the quality of life of patients. Topical dexamethasone (Dex) administration protects the cornea from the hyperosmotic stress (HS) induced by tears. Pyroptosis participates in the activation of epithelial inflammation during DED. However, it remains unclear whether Dex attenuates the progression of DED through pyroptosis. In this study, we aimed to investigate the effect of Dex on DED using both cell and animal models and its underlying mechanism. The inflammatory factors contained in tears were detected using a cytokine assay. The pyroptosis in DED mice and human corneal epithelial cells (HCECs) treated with hyperosmotic medium under various treatments was evaluated by immunohistochemical assays (IHC) or western blotting (WB). RNA expression was manipulated with siRNA or agomir microRNAs and measured using a polymerase chain reaction. The scratch assay was used to assess the migration rate of HCECs. Remaining corneal defects were evaluated using fluorescein staining and photographed using a digital camera. Dex could suppress the release of inflammatory factors and notably attenuate pyroptosis, KCNQ1OT1 expression, and NF-κB activation induced by HS injury in vivo and in vitro. KCNQ1OT1 upregulation could activate pyroptosis by sponging miR-214. Furthermore, KCNQ1OT1 knockdown and miR-214 overexpression reversed the effect of HS, promoted the migration of HCECs, and accelerated corneal wound healing. Dex effectively suppressed HS-induced pyroptosis through the KCNQ1OT1/miR-214/caspase-1 signaling axis by inhibiting the NF-κB activation. Our results provide a novel understanding of the mechanism of Dex as an anti-inflammatory drug in DED.
Keywords: Cornea; Dexamethasone; Dry eye; KCNQ1OT1; Migration; Pyroptosis.
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