Proceedings of the National Academy of Sciences - PNAS, 2011-07, Vol.108 (28), p.E279-E287
2011
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- Autor(en) / Beteiligte
- Titel
- Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2011-07, Vol.108 (28), p.E279-E287
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1100901108Titel-ID: cdi_proquest_miscellaneous_1093448352
- Format
- –
- Schlagworte
- Age, Alzheimer disease, Alzheimer's disease, Amyloid, Amyloid beta-Peptides - antagonists & inhibitors, Amyloid beta-Peptides - immunology, Amyloid beta-Peptides - metabolism, Animal models, Animals, Antibodies, Antibodies, Bispecific - administration & dosage, Antibodies, Bispecific - therapeutic use, Apolipoprotein E, Apolipoprotein E4 - genetics, beta -Amyloid, Biological Sciences, Blindness, Cells, cognition, Cognitive ability, complement, Complement System Proteins - metabolism, Deposits, diet, Dietary Fats - administration & dosage, Diets, Disease Models, Animal, dose response, Dose-Response Relationship, Immunologic, epithelium, Female, histopathology, Humans, Immunotherapy, Macular degeneration, Macular Degeneration - etiology, Macular Degeneration - pathology, Macular Degeneration - physiopathology, Macular Degeneration - therapy, Male, Mice, Mice, Inbred BALB C, Mice, Knockout, Mice, Transgenic, Neurodegenerative diseases, pathogenesis, Peptide Fragments - antagonists & inhibitors, Peptide Fragments - immunology, peptides, Plaques, PNAS Plus, Preservation, Retina, retinal pigment epithelium, Retinal Pigment Epithelium - metabolism, Retinal Pigment Epithelium - pathology, risk, Rodents, Vision, Vision, Low - physiopathology, Vision, Low - prevention & control, Visual perception