Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
The potential role of amyloid β in the pathogenesis of age-related macular degeneration
Takeshi Yoshida, … , Manabu Mochizuki, Ikuo Morita
Takeshi Yoshida, … , Manabu Mochizuki, Ikuo Morita
Published October 3, 2005
Citation Information: J Clin Invest. 2005;115(10):2793-2800. https://doi.org/10.1172/JCI24635.
View: Text | PDF
Research Article Angiogenesis

The potential role of amyloid β in the pathogenesis of age-related macular degeneration

  • Text
  • PDF
Abstract

Drusen are extracellular deposits that lie beneath the retinal pigment epithelium (RPE) and are the earliest signs of age-related macular degeneration (AMD). Recent proteome analysis demonstrated that amyloid β (Aβ) deposition was specific to drusen from eyes with AMD. To work toward a molecular understanding of the development of AMD from drusen, we investigated the effect of Aβ on cultured human RPE cells as well as ocular findings in neprilysin gene–disrupted mice, which leads to an increased deposition Aβ. The results showed that Aβ treatment induced a marked increase in VEGF as well as a marked decrease in pigment epithelium-derived factor (PEDF). Conditioned media from Aβ-exposed RPE cells caused a dramatic increase in tubular formation by human umbilical vein endothelial cells. Light microscopy of senescent neprilysin gene–disrupted mice showed an increased number of degenerated RPE cells with vacuoles. Electron microscopy revealed basal laminar and linear deposits beneath the RPE layer, but we did not observe choroidal neovascularization (CNV). The present study demonstrates that Aβ accumulation affects the balance between VEGF and PEDF in the RPE, and an accumulation of Aβ reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation. Some other factors, such as breakdown of integrity of Bruch membrane, might be necessary to induce CNV of AMD.

Authors

Takeshi Yoshida, Kyoko Ohno-Matsui, Shizuko Ichinose, Tetsuji Sato, Nobuhisa Iwata, Takaomi C. Saido, Toshio Hisatomi, Manabu Mochizuki, Ikuo Morita

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
Immunohistochemical detection of APP, neprilysin, and β-secretase in the...
Immunohistochemical detection of APP, neprilysin, and β-secretase in the RPE cell layer of albino ddY mice. Paraformaldehyde-fixed sections from eyeballs of male albino ddY mice were stained for APP (A), neprilysin (B), or β-secretase (C). Immune complexes were detected with DAB as a brown reaction product. Immunoreactivity for APP, neprilysin, and β-secretase was observed in the RPE cell layer. DAB staining was absent when nonimmune serum was substituted for the primary antibody (D). Scale bars: 20 μm (A–D). ONL, outer nuclear layer; OS, outer segment.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts