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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.
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Research Article Angiogenesis

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

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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

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Figure 5

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Light microscopy of H&E-stained sections of 27-month-old neprilysin-...
Light microscopy of H&E-stained sections of 27-month-old neprilysin-deficient (B and D) and age-matched wild-type (A and C) mice retinas. C and D show magnified views of A and B, respectively. (A and C) Morphology of normal retina from age-matched wild-type mice. (B and D) Morphology of senescent neprilysin-deficient mice showing degenerated cells with vacuoles in the RPE layer (arrowheads). Scale bars: 150 μm (A and B); 30 μm (C and D).
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