Role of matrix metalloproteinase-9 in angiogenesis caused by ocular infection with herpes simplex virus
S Lee, M Zheng, B Kim, BT Rouse - The Journal of clinical …, 2002 - Am Soc Clin Investig
S Lee, M Zheng, B Kim, BT Rouse
The Journal of clinical investigation, 2002•Am Soc Clin InvestigIn this report, we demonstrate that herpes simplex virus (HSV) infection of the cornea results
in the upregulation of the matrix-degrading metalloproteinase enzyme MMP-9. This enzyme
was shown to contribute to the neovascularization process that occurs in the corneal stroma
in response to HSV infection. The likely source of MMP-9, at least initially after infection, was
neutrophils that were signaled to invade the cornea soon after infection. Corneal infiltrating
neutrophils were shown to express MMP-9, and preventing the neutrophil response with …
in the upregulation of the matrix-degrading metalloproteinase enzyme MMP-9. This enzyme
was shown to contribute to the neovascularization process that occurs in the corneal stroma
in response to HSV infection. The likely source of MMP-9, at least initially after infection, was
neutrophils that were signaled to invade the cornea soon after infection. Corneal infiltrating
neutrophils were shown to express MMP-9, and preventing the neutrophil response with …
In this report, we demonstrate that herpes simplex virus (HSV) infection of the cornea results in the upregulation of the matrix-degrading metalloproteinase enzyme MMP-9. This enzyme was shown to contribute to the neovascularization process that occurs in the corneal stroma in response to HSV infection. The likely source of MMP-9, at least initially after infection, was neutrophils that were signaled to invade the cornea soon after infection. Corneal infiltrating neutrophils were shown to express MMP-9, and preventing the neutrophil response with specific mAb diminished MMP-9 expression as well as the extent of angiogenesis. Further supporting a role for MMP-9 in HSV-induced corneal angiogenesis was the observation that inhibition of MMP-9 with the specific inhibitor TIMP-1 resulted in reduced angiogenesis. In addition, angiogenesis was diminished in ocularly infected MMP-9 knockout mice. Our results demonstrate that MMP-9 is involved in angiogenesis caused by HSV. Since angiogenesis appears to represent a vital step in the pathogenesis of herpetic stromal keratitis, these results indicate that targeting MMP-9 for inhibition should prove useful for the therapy of herpetic stromal keratitis.
The Journal of Clinical Investigation