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

ABSTRACT: Age-related macular degeneration (AMD) is a leading cause of visual dysfunction worldwide. Amyloid ? (A?) peptides, A?1-40 (A?40) and A?1-42 (A?42), have been implicated previously in the AMD disease process. Consistent with a pathogenic role for A?, 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 A?-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 A?40 and A?42. Concomitant reduction in the levels of A? and activated complement components in sub-RPE deposits and structural preservation of the RPE are associated with anti-A?40/42 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-A? antibodies. They also implicate A? in the pathogenesis of AMD and identify A? as a viable therapeutic target for its treatment.

SUBMITTER: Ding JD 

PROVIDER: S-EPMC3136266 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature