EMMPRIN is Upregulated During Herpes Simplex Virus (HSV) Corneal Infection in vivo

Abstract

Abstract: : Purpose: Herpetic stromal keratitis (HSK) is a condition that can result in dissolution of the stroma and blindness. Stromal dissolution is largely controlled by matrix metalloproteinases (MMPs) which degrade collagen and other proteins of the extracellular matrix. As previously reported, MMP expression is induced by extracellular matrix metalloproteinase inducer (EMMPRIN). We investigated EMMPRIN expression in the murine cornea during HSV infection. Methods: HSK was induced in the eyes of BALB/C6 mice either by topical application of HSV strain K19 directly onto scratched corneas or by injection of virus into the trigeminal ganglion. Corneas were harvested 1 and 5 days post infection. EMMPRIN mRNA expression was assessed by in situ hybridization in the scratch model while EMMPRIN protein expression was examined by immunohistochemistry in the trigeminal injection model. Results: Scratched mouse corneas infected with HSV showed increased EMMPRIN mRNA expression in both epithelial and endothelial cell layers compared to controls. Staining was more intense in endothelial cells. Immunocytochemical staining for EMMPRIN revealed marked up-regulation of the protein in infected corneas as compared to control eyes. Signal was present in both epithelial and endothelial cells. Conclusion: This study demonstrates that EMMPRIN is expressed in the mouse cornea and is upregulated during corneal HSV infection. Studies to examine the mechanism(s) responsible for increased EMMPRIN expression and the role of EMMPRIN in regulating corneal MMPs during the chronic inflammation associated with HSK are underway.

Keywords: herpes simplex virus • keratitis • cornea: basic science