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Temporal release of matrix metalloproteinases in human microbial keratitis

Temporal release of matrix metalloproteinases in human microbial keratitis
Temporal release of matrix metalloproteinases in human microbial keratitis
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.
0146-0404
Afshar, M.F.
40e80a6d-3b24-4673-8c0c-a9d0716eb554
wong, yuk
1f0c1dc4-52d4-4925-9d2f-3458fd0fb0bc
Pender, Sylvia
62528b03-ec42-41bb-80fe-48454c2c5242
Hossain, Parwez
563de5fc-84ad-4539-9228-bde0237eaf51
Afshar, M.F.
40e80a6d-3b24-4673-8c0c-a9d0716eb554
wong, yuk
1f0c1dc4-52d4-4925-9d2f-3458fd0fb0bc
Pender, Sylvia
62528b03-ec42-41bb-80fe-48454c2c5242
Hossain, Parwez
563de5fc-84ad-4539-9228-bde0237eaf51

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).

Record type: Meeting abstract

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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More information

Published date: April 2009

Identifiers

Local EPrints ID: 448127
URI: http://eprints.soton.ac.uk/id/eprint/448127
ISSN: 0146-0404
PURE UUID: fb5d68dc-07cd-485c-a4b8-c288c960fd75
ORCID for Sylvia Pender: ORCID iD orcid.org/0000-0001-6332-0333
ORCID for Parwez Hossain: ORCID iD orcid.org/0000-0002-3131-2395

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Date deposited: 01 Apr 2021 15:59
Last modified: 13 Apr 2021 01:41

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Contributors

Author: M.F. Afshar
Author: yuk wong
Author: Sylvia Pender ORCID iD
Author: Parwez Hossain ORCID iD

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