Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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.
Conclusions: :
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.
Keywords: age-related macular degeneration • choroid: neovascularization • Bruch's membrane