The diurnal variation of matrix metalloproteinase-9 and its associated factors in human tears

Markoulli, M; Papas, E; Cole, N; Holden, BA

The diurnal variation of matrix metalloproteinase-9 and its associated factors in human tears

Markoulli, M Papas, E Cole, N

Holden, BA

Permalink

Publication Type:: Journal Article
Citation:: Investigative Ophthalmology and Visual Science, 2012, 53 (3), pp. 1479 - 1484
Issue Date:: 2012-03-01

Closed Access

	Filename	Description	Size
	z7g00312001479 (1).pdf	Published Version	176.18 kB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Markoulli, M	en_US
dc.contributor.author	Papas, E	en_US
dc.contributor.author	Cole, N https://orcid.org/0000-0002-9866-4694	en_US
dc.contributor.author	Holden, BA	en_US
dc.date.issued	2012-03-01	en_US
dc.identifier.citation	Investigative Ophthalmology and Visual Science, 2012, 53 (3), pp. 1479 - 1484	en_US
dc.identifier.issn	0146-0404	en_US
dc.identifier.uri	http://hdl.handle.net/10453/115597
dc.description.abstract	PURPOSE. Matrix metalloproteinases (MMPs) are degrading enzymes which maintain and remodel tissue architecture. Upregulation of MMP-9 has been associated with corneal erosions and ulceration. As these conditions are often exacerbated on waking, suggesting that degrading activity is upregulated overnight, this study set out to determine the diurnal variation of MMP-9, Tissue Inhibitor of Metalloproteinase (TIMP)-1, and Neutrophil Gelatinase-Associated Lipocalin (NGAL). METHODS. Flush tears were collected from 46 healthy, noncontact lens wearers at midday, before sleep, and immediately on waking. Total protein content (TPC) was measured using the bicinchoninic acid method, and MMP-9, TIMP-1, and NGAL concentrations were measured using sandwich enzyme-linked immunoassay. Statistical analysis was performed using repeated measures analysis of variance. RESULTS. TPC was 3.4 ± 1.5 mg/mL, 5.0 ± 3.7 mg/mL and 15.5 ± 8.4 mg/mL for midday, before sleep, and on waking respectively, the latter being significantly greater than the other two (P < 0.001). MMP-9 concentrations at the corresponding time points were 9.8 ± 14.3 ng/mL, 8.5 ± 11.7 ng/mL, and 2000.7 ± 1950.7 ng/mL. Again, the value on waking was significantly greater than the previous two visits (P < 0.001). TIMP-1 concentrations exceeded those of MMP-9 at midday but the ratio of the two reversed on awakening. CONCLUSIONS. Concentrations of MMP-9 are negligible during the day and completely inhibited by TIMP-1. On awakening, MMP-9 increases 200-fold, an increase that is not completely inhibited by TIMP-1. This diurnal change, along with the presence of NGAL which protects MMP-9 from degradation, suggests that the closed eye is an environment conducive to extracellular matrix remodeling. © 2012 The Association for Research in Vision and Ophthalmology, Inc.	en_US
dc.relation.ispartof	Investigative Ophthalmology and Visual Science	en_US
dc.relation.isbasedon	10.1167/iovs.11-8365	en_US
dc.subject.classification	Ophthalmology & Optometry	en_US
dc.subject.mesh	Tears	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Acute-Phase Proteins	en_US
dc.subject.mesh	Proto-Oncogene Proteins	en_US
dc.subject.mesh	Tissue Inhibitor of Metalloproteinase-1	en_US
dc.subject.mesh	Enzyme-Linked Immunosorbent Assay	en_US
dc.subject.mesh	Analysis of Variance	en_US
dc.subject.mesh	Prospective Studies	en_US
dc.subject.mesh	Reproducibility of Results	en_US
dc.subject.mesh	Circadian Rhythm	en_US
dc.subject.mesh	Adolescent	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Matrix Metalloproteinase 9	en_US
dc.subject.mesh	Lipocalins	en_US
dc.subject.mesh	Young Adult	en_US
dc.subject.mesh	Biomarkers	en_US
dc.subject.mesh	Lipocalin-2	en_US
dc.title	The diurnal variation of matrix metalloproteinase-9 and its associated factors in human tears	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	53	en_US
utslib.for	11 Medical and Health Sciences	en_US
utslib.for	06 Biological Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	53	en_US

Abstract:

PURPOSE. Matrix metalloproteinases (MMPs) are degrading enzymes which maintain and remodel tissue architecture. Upregulation of MMP-9 has been associated with corneal erosions and ulceration. As these conditions are often exacerbated on waking, suggesting that degrading activity is upregulated overnight, this study set out to determine the diurnal variation of MMP-9, Tissue Inhibitor of Metalloproteinase (TIMP)-1, and Neutrophil Gelatinase-Associated Lipocalin (NGAL). METHODS. Flush tears were collected from 46 healthy, noncontact lens wearers at midday, before sleep, and immediately on waking. Total protein content (TPC) was measured using the bicinchoninic acid method, and MMP-9, TIMP-1, and NGAL concentrations were measured using sandwich enzyme-linked immunoassay. Statistical analysis was performed using repeated measures analysis of variance. RESULTS. TPC was 3.4 ± 1.5 mg/mL, 5.0 ± 3.7 mg/mL and 15.5 ± 8.4 mg/mL for midday, before sleep, and on waking respectively, the latter being significantly greater than the other two (P < 0.001). MMP-9 concentrations at the corresponding time points were 9.8 ± 14.3 ng/mL, 8.5 ± 11.7 ng/mL, and 2000.7 ± 1950.7 ng/mL. Again, the value on waking was significantly greater than the previous two visits (P < 0.001). TIMP-1 concentrations exceeded those of MMP-9 at midday but the ratio of the two reversed on awakening. CONCLUSIONS. Concentrations of MMP-9 are negligible during the day and completely inhibited by TIMP-1. On awakening, MMP-9 increases 200-fold, an increase that is not completely inhibited by TIMP-1. This diurnal change, along with the presence of NGAL which protects MMP-9 from degradation, suggests that the closed eye is an environment conducive to extracellular matrix remodeling. © 2012 The Association for Research in Vision and Ophthalmology, Inc.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/115597