Systemic Administration of Abeta mAb Reduces Retinal Deposition of Abeta and Activated Complement C3 in Age-Related Macular Degeneration Mouse ModelReport as inadecuate




Systemic Administration of Abeta mAb Reduces Retinal Deposition of Abeta and Activated Complement C3 in Age-Related Macular Degeneration Mouse Model - Download this document for free, or read online. Document in PDF available to download.

Age-related macular degeneration AMD is a leading cause of legal blindness in the Western world. There are effective treatments for the vascular complications of neo-vascular AMD, but no effective therapies are available for the dry-atrophic form of the disease. A previously described transgenic CFH-gene deficient mouse model, cfh−-−, shows hallmarks of early AMD. The ocular phenotype has been further analysed to demonstrate amyloid beta Aβ rich basement membrane deposits associated with activated complement C3. Cfh−-− mice were treated systemically in both prophylactic and therapeutic regimes with an anti-Aβ monoclonal antibody mAb, 6F6, to determine the effect on the cfh−-− retinal phenotype. Prophylactic treatment with 6F6 demonstrated a dose dependent reduction in the accumulation of both Aβ and activated C3 deposition. A similar reduction in the retinal endpoints could be seen after therapeutic treatment. Serum Aβ levels after systemic administration of 6F6 show accumulation of Aβ in the periphery suggestive of a peripheral sink mechanism. In summary, anti-Aβ mAb treatment can partially prevent or reverse ocular phenotypes of the cfh−-− mouse. The data support this therapeutic approach in humans potentially modulating two key elements in the pathogenesis of AMD – Aβ and activated, complement C3.



Author: Ian Catchpole , Volker Germaschewski , Jaimie Hoh Kam , Peter Lundh von Leithner, Susannah Ford, Gerald Gough, Peter Adamson, Phi

Source: http://plos.srce.hr/



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