May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Amyloid-β Regulates the Gene Expression Profile of Matrix Metalloproteinases in Human Retinal Pigment Epithelial Cells
Author Affiliations & Notes
  • T. Yoshida
    Tokyo Medical & Dental University, Tokyo, Japan
    Ophthalmology & Visual Science,
  • K. Ohno-Matsui
    Tokyo Medical & Dental University, Tokyo, Japan
    Ophthalmology & Visual Science,
  • J. Wang
    Tokyo Medical & Dental University, Tokyo, Japan
    Ophthalmology & Visual Science,
  • N. Shimada
    Tokyo Medical & Dental University, Tokyo, Japan
    Ophthalmology & Visual Science,
  • I. Morita
    Tokyo Medical & Dental University, Tokyo, Japan
    Cellular Biology and Chemistry,
  • M. Mochizuki
    Tokyo Medical & Dental University, Tokyo, Japan
    Ophthalmology & Visual Science,
  • Footnotes
    Commercial Relationships  T. Yoshida, None; K. Ohno-Matsui, None; J. Wang, None; N. Shimada, None; I. Morita, None; M. Mochizuki, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 221. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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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 
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