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DO Clegg, ST Leu, S Batni, MJ Radeke, LV Johnson, DH Anderson; Drusen are Cold Spots for Proteolysis: Expression of Matrix Metalloproteinases and Their Tissue Inhibitor Proteins in Age-related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):697.
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Purpose: The purpose of this study was to examine the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in drusen, and in the surrounding cells and tissues. Methods: To assess the extent of MMP and TIMP expression by retinal pigment epithelial (RPE) cells, cDNA arrays were screened with probes generated from cultured human RPE. The distribution of MMPs1-3 and TIMPs1-4 was determined using immunohistochemistry. Gelatinase activity was assessed in unfixed frozen sections using in situ zymography. Results: In cultured RPE, expression of 10 MMP and all 4 TIMP mRNA was detected. MMP immunoreactivity was widespread in RPE-choroid, but was absent from the drusen interior. TIMP-3, but not other TIMPS, was detected in the drusen interior. Likewise, metal ion dependent gelatinase activity could be detected in RPE-choroid, but not in drusen. Conclusion: These results show that, while metalloproteinase activity is widepread throughout the RPE-choroid, drusen are cold spots for proteolysis. This leads to the speculation that TIMP-3 accumulation within drusen could inhibit MMPs and as a result slow the proteolytic degradation of these deposits.
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