Temporal release of matrix metalloproteinases in human microbial keratitis

Afshar, M.F., wong, yuk, Pender, Sylvia and Hossain, Parwez (2009) Temporal release of matrix metalloproteinases in human microbial keratitis. Investigative Ophthalmology & Visual Science, 50 (13).

Abstract

Purpose: : Microbial keratitis (MK) is a leading cause of blindness, affecting 2 million people worldwide each year. Excess inflammatory response can lead to sight threatening tissue destruction through cytokine mediated production of matrix metalloproteinases (MMP). MMPs are proteolytic enzymes which degrade and remodel the extracellular matrix and their expression is associated with increased severity of corneal ulceration in pseudomonal keratitis. However, the release of the enzymes in the course of human disease is not known. Our aim was to evaluate the MMP profile of human MK and assess how this changes with treatment of MK.

Methods: : Tear Samples were collected from 3 patients with MK and 3 controls. . Simultaneous analysis of MMP-1, MMP-3 and MMP-9 were performed using special multiplexed immunoassays. The mean levels of MMP-1, MMP-3 and MMP-9 were measured in both patient groups at day 1, 3, 7 and 14 post diagnosis.

Results: : At day 1 the predominant MMP identified was MMP-9 with mean concentration of 9502.9 ng/ml in MK patients compared to controls. At day 3 MMP-9 levels reduced to 1357.7 ng/ml, falling further to 541.3ng/ml at day 7. At Day 14 the levels were 647.7ng/ml. MMP-1 levels showed no significant difference between MK patients and controls (96.8ng/ml vs 109.8ng/ml). MMP-3 levels were 83.3ng/ml in controls and increased to 192.9ng/ml in MK patients. At day 3 the MMP-3 concentrations in MK patients reduced to sub control levels (24.6ng/ml).

Conclusions: : These results show for the first time the relationship of MMP-9 expression with the clinical course of disease. The data indicate that the highest levels of MMPs occur on the day of presentation returning to baseline levels by day 7, suggesting that therapies designed to halt tissue damage need to be effective in the early stages of disease.

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Contributors

Author: Sylvia Pender

Author: Parwez Hossain

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