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T. Yoshida, K. Ohno-Matsui, J. Wang, N. Shimada, I. Morita, M. Mochizuki; Amyloid-β Regulates the Gene Expression Profile of Matrix Metalloproteinases in Human Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):221.
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We have recently reported that the senescent neprilysin gene-disrupted mice reproduced similar features of human age-related macular degeneration (AMD), however, choroidal neovascularization (CNV) did not developed in these mice (JCI, 2005). The breakdown of Bruch’s membrane is considered a pivotal step for the development of CNV, therefore we investigated the gene expression profile of Matrix Metalloproteinases (MMPs) induced by Aβ in human RPE cells.
RPE cells were treated with Aβ for 24 h. The gene expression of MMP-2, MMP-9 and MT1-MMP in RPE was analyzed using real-time PCR. MMP-2 in conditioned medium was also analyzed using ELISA.
Aβ treatment did not induce a significant increase the total amount of MMP-2 and MMP-9 at mRNA as well as protein level, however, a significant increase of active MMP-2 was detected by ELISA. Correspondingly real-time PCR revealed the up-regulation of MT1-MMP.
These suggest that Aβ activates MMP-2 via up-regulation of its activation enzyme: MT1-MMP in RPE. These changes might modulate the degradation of Bruch’s membrane and play a critical role in the development of CNV in AMD.
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