Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration.

Journal Article (Journal Article)

Age-related macular degeneration (AMD) is a leading cause of visual dysfunction worldwide. Amyloid β (Aβ) peptides, Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42), have been implicated previously in the AMD disease process. Consistent with a pathogenic role for Aβ, we show here that a mouse model of AMD that invokes multiple factors that are known to modify AMD risk (aged human apolipoprotein E 4 targeted replacement mice on a high-fat, cholesterol-enriched diet) presents with Aβ-containing deposits basal to the retinal pigmented epithelium (RPE), histopathologic changes in the RPE, and a deficit in scotopic electroretinographic response, which is reflective of impaired visual function. Strikingly, these electroretinographic deficits are abrogated in a dose-dependent manner by systemic administration of an antibody targeting the C termini of Aβ40 and Aβ42. Concomitant reduction in the levels of Aβ and activated complement components in sub-RPE deposits and structural preservation of the RPE are associated with anti-Aβ40/42 antibody immunotherapy and visual protection. These observations are consistent with the reduction in amyloid plaques and improvement of cognitive function in mouse models of Alzheimer's disease treated with anti-Aβ antibodies. They also implicate Aβ in the pathogenesis of AMD and identify Aβ as a viable therapeutic target for its treatment.

Full Text

Duke Authors

Cited Authors

  • Ding, J-D; Johnson, LV; Herrmann, R; Farsiu, S; Smith, SG; Groelle, M; Mace, BE; Sullivan, P; Jamison, JA; Kelly, U; Harrabi, O; Bollini, SS; Dilley, J; Kobayashi, D; Kuang, B; Li, W; Pons, J; Lin, JC; Bowes Rickman, C

Published Date

  • July 12, 2011

Published In

Volume / Issue

  • 108 / 28

Start / End Page

  • E279 - E287

PubMed ID

  • 21690377

Pubmed Central ID

  • PMC3136266

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1100901108


  • eng

Conference Location

  • United States