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UM SchloetzerSchrehardt, M Zenkel, J Lommatzsch, M Kuechle, AG P Konstas, GO H Naumann; Altered Balance Between Matrix Metalloproteinases And Their Inhibitors In Pseudoexfoliation Syndrome And Pseudoexfoliation Glaucoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3369.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To assess the expression and activities of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the abnormal matrix process characteristic of pseudoexfoliation (PEX) syndrome. Methods: Expression of 7 members of the MMP family and 3 TIMPs was evaluated in anterior segment tissues of PEX eyes and control eyes by immunohistochemistry, semiquantitative RT-PCR, and suppression subtractive hybridization and differential screening. In addition, MMP and TIMP levels and activities were analyzed in aqueous humor and serum of patients with PEX syndrome or PEX glaucoma and control patients with cataract or primary open-angle glaucoma using zymography, Western Blotting, enzyme immunoassays, and activity assays. Results: Whereas expression of MMP-1, -3, -7, -9, -12, and -14 showed no differences, expression of MMP-2 and TIMP-2 was significantly increased (2-and 4-fold, respectively) in anterior segment tissues of PEX eyes as compared to control eyes both on the protein and mRNA level. In contrast, TIMP-1 expression was decreased, and TIMP-3 expression was unchanged. Prominent immunoreactivity of TIMP-1, -2, and -3 was associated with the pathologic extracellular matrix deposits in PEX eyes. Total levels of MMP-2, TIMP-1, and TIMP-2 were significantly increased in aqueous humor samples of PEX eyes as compared to control eyes, whereas serum levels were not significantly different. However, the ratio of active/ latent forms of MMP-2 was significantly decreased in PEX samples as compared to control samples, which appears to result from the formation of MMP/TIMP complexes. TIMP levels in aqueous humor correlated significantly with total aqueous protein concentrations. MMP-1, -7, and -9 were below detection limit in most aqueous samples. Conclusion: The surplus of TIMPs and the decreased ratio of active/latent forms of MMP-2 in the aqueous humor of PEX eyes leads to a local proteolytic imbalance, which may underly the pathogenetic mechanisms and contribute to the stable deposition of abnormal extracellular material in the trabecular meshwork and other anterior segment tissues in PEX syndrome and PEX glaucoma.
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