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Li Guo, Ali A. Hussain, G. Astrid Limb, John Marshall; Age-Dependent Variation in Metalloproteinase Activity of Isolated Human Bruch’s Membrane and Choroid. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2676-2682.
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purpose. To characterize and determine the effect of aging on the matrix
metalloproteinase (MMP) component of the extracellular
matrix–remodeling mechanism of isolated human Bruch’s–choroid.
methods. Immunohistochemical techniques and western blot analysis were used to
detect and localize various members of the MMP family of proteolytic
enzymes in the Bruch’s–choroid complex. Gelatin substrate zymography
was used to detect and quantify the levels of MMP-2 and -9 in
homogenates of Bruch’s–choroid from both macular and peripheral
regions of the human fundus. Aging alterations in these enzymes were
quantified by densitometric analysis of photographic negatives of the
results. Intact preparations of Bruch’s–choroid showed the presence of
inactive forms of two gelatinases (MMP-2, 65 kDa, and MMP-9, 92 kDa),
interstitial collagenase (MMP-1, 52 kDa) and stromelysin (MMP-3, 57
kDa). MMP-1 and -3 were localized primarily to Bruch’s membrane. MMP-9
was distributed evenly in Bruch’s membrane with some patchy presence
in the choroidal mass. Distribution of MMP-2 was similar to that of
MMP-9, but the staining in Bruch’s was much fainter. On gelatin
zymography, an active form of MMP-2 (58-kDa species) was frequently
observed in peripheral samples but only occasionally in macular
regions. The levels of MMP-2 and -9 increased with aging in both the
macular and the peripheral regions of the fundus (P < 0.05). MMP-2 levels were lower in macular regions than in the
periphery but no such variation was observed with MMP-9. Both these
inactive gelatinases could be activated in vitro.
conclusions. A matrix-degrading mechanism essential for extracellular remodeling was
shown to be present in Bruch’s membrane. In macular regions,
increasing levels of inactive forms of metalloproteinase and scarcity
of active forms of MMP-2 suggests possible involvement of impaired
extracellular degradation in both aging and macular
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