| First Author | Ding JD | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 28 | Pages | E279-87 |
| PubMed ID | 21690377 | Mgi Jnum | J:174301 |
| Mgi Id | MGI:5056239 | Doi | 10.1073/pnas.1100901108 |
| Citation | Ding JD, et al. (2011) Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration. Proc Natl Acad Sci U S A 108(28):E279-87 |
| abstractText | Age-related macular degeneration (AMD) is a leading cause of visual dysfunction worldwide. Amyloid beta (Abeta) peptides, Abeta1-40 (Abeta40) and Abeta1-42 (Abeta42), have been implicated previously in the AMD disease process. Consistent with a pathogenic role for Abeta, 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 Abeta-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 Abeta40 and Abeta42. Concomitant reduction in the levels of Abeta and activated complement components in sub-RPE deposits and structural preservation of the RPE are associated with anti-Abeta40/42 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-Abeta antibodies. They also implicate Abeta in the pathogenesis of AMD and identify Abeta as a viable therapeutic target for its treatment. |
