NDLI: Increased sequestration of matrix metalloproteinases in ageing human Bruch's membrane: implications for ECM turnover.

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Increased sequestration of matrix metalloproteinases in ageing human Bruch's membrane: implications for ECM turnover.

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Increased sequestration of matrix metalloproteinases in ageing human Bruch's membrane: implications for ECM turnover.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	El-Osta, Austen Kumar, Anupma Hussain, Ali A. Marshall, John
Description	Country affiliation: United kingdom Author Affiliation: Kumar A ( Department of Ophthalmology, The Rayne Institute, St. Thomas' Hospital, London, United Kingdom. anupmakumar@hotmail.com)
Abstract	PURPOSE: The ageing of Bruch's membrane is associated with progressive reduction in the degradation of the capacity for ECM turnover mediated by the matrix metalloproteinase (MMP) system. In this study, the free and bound pools of all gelatinase species were quantified to aid in assessing the likelihood of reduced availability of pro-MMPs for activation in ageing Bruch's membrane. METHODS: Bruch's membrane from macular locations (10 eyes; donor age range, 21-84 years) was mounted in Ussing chambers and eluted with phosphate-buffered saline to release the free pool of MMPs. Free and bound pools of MMPs were subjected to gelatin zymography, and individual gelatinase species were quantified by densitometric scans. RESULTS: The zymograms displayed six gelatinase species: four corresponding to the pro- and active forms of MMP-2 and -9 and two high-molecular-weight polymeric forms designated HMW1 and -2, corresponding to approximate molecular masses of 195 and 391 kDa, respectively. The ageing of Bruch's membrane was associated with an exponential increase in the percentage of pro-MMPs bound to the membrane (pro-MMP-2: %age bound = 0.54 exp(0.04 x age), r = 0.87, P < 0.01; and pro-MMP-9: %age bound = 5.0 exp(0.03 x age), r = 0.8, P < 0.01). A similar exponential increase was seen in the percentage of bound HMW1 species (%bound = 11.7 exp(0.018 x age; P < 0.05). The HMW2 species was virtually all bound to the membrane, but some release was observed in the very elderly. CONCLUSIONS: The ageing of Bruch's membrane was associated with progressive sequestration of MMPs reducing the free concentration and potential for activation. These changes may underlie the reduction in degradation that leads to the age-related increase in the thickness of the membrane.
ISSN	01460404
e-ISSN	15525783
Journal	Investigative Opthalmology & Visual Science
Issue Number	5
Volume Number	51
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2010-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Aging Physiology Bruch Membrane Enzymology Extracellular Matrix Metabolism Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Densitometry Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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