MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions

Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix‐metalloproteinases (MMPs ‐1,‐3,‐9,‐13), IL‐1β and IL‐6, while it significantly increased MMP‐8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP‐8 induction is responsible for some of the protective effects of Dex in CM, MMP‐8 knock out mice (MMP‐8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 μl of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP‐8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP‐8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL‐6, CXCL1, and MMP‐1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP‐8KO mice. These results suggest that some of the anti‐inflammatory effects of Dex are mediated through increased MMP‐8 expression. J. Cell. Physiol. 231: 2506–2516, 2016. © 2016 Wiley Periodicals, Inc.