Publications [#264413] of Sina Farsiu

Papers Published

1. 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, 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, vol. 108 no. 28 (July, 2011), pp. E279-E287, ISSN 1091-6490 [21690377], [doi]
   (last updated on 2024/12/31)

   Abstract:
   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.

   Keywords:
   Amyloid beta-Peptides • Animals • Antibodies, Bispecific • Apolipoprotein E4 • Complement System Proteins • Dietary Fats • Disease Models, Animal • Dose-Response Relationship, Immunologic • Female • Humans • Immunotherapy • Macular Degeneration • Male • Mice • Mice, Inbred BALB C • Mice, Knockout • Mice, Transgenic • Peptide Fragments • Retinal Pigment Epithelium • Vision, Low • administration & dosage • antagonists & inhibitors • antagonists & inhibitors* • etiology • genetics • immunology • metabolism • metabolism* • pathology • pathology* • physiopathology • prevention & control • therapeutic use • therapy*