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S.A. McClellan, X. Huang, L. Hazlett; Role of MMP–9 in Bacterial Keratitis . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5081.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the role of matrix metalloproteinase 9 (MMP–9) in P. aeruginosa keratitis. Methods: Gene array was used to determine corneal MMP–9 mRNA levels in susceptible C57BL/6 (B6) and resistant BALB/c mice. BALB/c mice also were injected (subconjunctivally and i.p.) with rMMP–9 protein and disease graded at 1–5 days p.i. PMN were quantitated by MPO assay and Langerhans cells (LC) quantitated using ADPase staining. Similar assays were done using B6 mice injected with a MMP–9 neutralizing Ab and in MMP–9 knockout mice. Results: Microarray revealed that mRNA levels increased 32.8 in B6 vs. 5.5 fold in BALB/c mice at 1 day p.i. Treatment of BALB/c mice with rMMP–9 produced significantly greater disease at 1–5 days p.i. compared to PBS controls. PMN and LC number also were significantly elevated in the cornea of rMMP–9 vs. PBS treated mice after infection. In contrast, neutralization of MMP–9 in B6 mice resulted in significantly reduced disease scores, number of PMN and LC. MMP–9 knockout mice also showed significantly less LC infiltration in the corneal epithelium compared to wt mice. Conclusions: MMP–9 is an important component of the inflammatory response. When added exogenously to normally resistant mice, it increased the number of PMN and LC in the infected cornea and resulted in more severe disease. Inhibition of MMP–9 in susceptible mice improved disease, prevented (or extended) time to perforation and reduced the number of infiltrating PMN and LC. Regimens aimed at regulation of MMP–9 in the cornea after infection may provide novel therapy for treatment of bacterial infection.
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