Amyloid-beta(1-42) alters structure and function of retinal pigmented epithelial cells

Aging Cell. 2009 Apr;8(2):162-77. doi: 10.1111/j.1474-9726.2009.00456.x. Epub 2009 Feb 23.


Age-related macular degeneration (AMD) is characterized by the formation of drusen, extracellular deposits associated with atrophy of the retinal pigmented epithelium (RPE), disturbance of the transepithelial barrier and photoreceptor death. Amyloid-beta (Abeta) is present in drusen but its role during AMD remains unknown. This study investigated the in vitro and in vivo effects of the oligomeric form of Abeta(1-42) - OAbeta(1-42) - on RPE and found that it reduced mitochondrial redox potential and increased the production of reactive oxygen species, but did not induce apoptosis in RPE cell cultures. It also disorganized the actin cytoskeleton and halved occludin expression, markedly decreasing attachment capacity and abolishing the selectivity of RPE cell transepithelial permeability. Antioxidant pretreatment partially reversed the effects of OAbeta(1-42) on mitochondrial redox potential and transepithelial permeability. Subretinally injected OAbeta(1-42) induced pigmentation loss and RPE hypertrophy but not RPE cell apoptosis in C57BL/6 J mice. Rapid OAbeta(1-42)-induced disorganization of cytoskeletal actin filaments was accompanied by decreased RPE expression of the tight junction proteins occludin and zonula occludens-1 and of the visual cycle proteins cellular retinaldehyde-binding protein and RPE65. The number of photoreceptors decreased by half within a few days. Our study pinpoints the role of Abeta in RPE alterations and dysfunctions leading to retinal degeneration and suggests that targeting Abeta may help develop selective methods for treating diseases involving retinal degeneration, such as AMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Aging / pathology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Carrier Proteins / drug effects
  • Carrier Proteins / metabolism
  • Cell Line
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Cytoskeleton / pathology
  • Eye Proteins / drug effects
  • Eye Proteins / metabolism
  • Humans
  • Hypertrophy / chemically induced
  • Hypertrophy / metabolism
  • Hypertrophy / physiopathology
  • Macular Degeneration / chemically induced
  • Macular Degeneration / metabolism
  • Macular Degeneration / physiopathology*
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / physiology
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Peptide Fragments / metabolism
  • Peptide Fragments / toxicity*
  • Photoreceptor Cells, Vertebrate / drug effects
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / pathology
  • Reactive Oxygen Species / metabolism
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / pathology*
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism
  • Tight Junctions / pathology
  • cis-trans-Isomerases


  • Amyloid beta-Peptides
  • Carrier Proteins
  • Eye Proteins
  • Peptide Fragments
  • Reactive Oxygen Species
  • amyloid beta-protein (1-42)
  • retinoid isomerohydrolase
  • cis-trans-Isomerases