April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Systemic Administration Of An Anti-amyloid Beta Monoclonal Antibody Interferes With The Ocular Pathology Of A Mouse Model Of Age-related Macular Degeneration (AMD) / Retinal Dysfunction
Author Affiliations & Notes
  • Ian R. Catchpole
    Topical BDU BioPharm R & D,
    GSK Med Rsch Ctr, Stevenage, United Kingdom
  • Volker Germaschewski
    Topical BDU BioPharm R & D,
    GSK Med Rsch Ctr, Stevenage, United Kingdom
  • Susannah Ford
    Topical BDU BioPharm R & D,
    GSK Med Rsch Ctr, Stevenage, United Kingdom
  • Gerald Gough
    Topical BDU BioPharm R & D,
    GSK Med Rsch Ctr, Stevenage, United Kingdom
  • Philip Overend
    Discovery Biometrics BioPharm,
    GSK Med Rsch Ctr, Stevenage, United Kingdom
  • Peter Adamson
    Ophthiris,
    GSK Med Rsch Ctr, Stevenage, United Kingdom
  • Peter Lundh von Leithner
    Institute of Ophthalmology, UCL, London, United Kingdom
  • Jaimie Hoh Kam
    Institute of Ophthalmology, UCL, London, United Kingdom
  • Pete Coffey
    Institute of Ophthalmology, UCL, London, United Kingdom
  • Glen Jeffery
    Institute of Ophthalmology, UCL, London, United Kingdom
  • Footnotes
    Commercial Relationships  Ian R. Catchpole, GSK (E); Volker Germaschewski, GSK (E); Susannah Ford, GSK (E); Gerald Gough, GSK (E); Philip Overend, GSK (E); Peter Adamson, GSK (E); Peter Lundh von Leithner, GSK (F); Jaimie Hoh Kam, GSK (F); Pete Coffey, GSK (F); Glen Jeffery, GSK (F)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1778. doi:
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      Ian R. Catchpole, Volker Germaschewski, Susannah Ford, Gerald Gough, Philip Overend, Peter Adamson, Peter Lundh von Leithner, Jaimie Hoh Kam, Pete Coffey, Glen Jeffery; Systemic Administration Of An Anti-amyloid Beta Monoclonal Antibody Interferes With The Ocular Pathology Of A Mouse Model Of Age-related Macular Degeneration (AMD) / Retinal Dysfunction. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1778.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Neovascular AMD has effective treatments, but no effective therapies are available for the dry/atrophic form of the disease. Data now support involvement of the alternative complement pathway in AMD development, particularly defects in complement factors H, (CFH) and B, (CFB). A transgenic CFH-gene deficient mouse model, (cfh-/-) shows hallmarks of early AMD - formation of ocular: autofluorescent basement membrane deposits with further retinal deposition of both activated complement C3 and amyloid beta. Cfh-/- mice were treated systemically in both prophylactic and therapeutic regimes with a GSK anti-amyloid beta monoclonal antibody (αAbeta mAb) to determine the effect on the cfh-/- retinal phenotype.

Methods: : Cfh-/- mice were treated at 3 months, (prophylaxis), and at 6 months, (therapy), weekly for 12 weeks. After treatment, efficacy end points, for both regimes were: quantification of retinal autofluorescent, basement membrane deposits by confocal scanning laser ophthalmoscope (cSLO) imaging, IHC analysis and quantification of retinal deposition of amyloid beta & activated complement C3, demonstration of elevated levels of total amyloid-ß protein / mAb complexes in sera.

Results: : Prophylactic treatment with a GSKαAbeta mAb demonstrated a dose dependent: Reduction in basement membrane deposits, reduction in amyloid beta and activated complement deposition, elevation in serum amyloid beta. A similar reduction in these endpoints could be seen after therapeutic treatment.

Conclusions: : Both prophylactic and therapeutic regimes with a GSK αAbeta mAb demonstrate that ocular phenotypes of the cfh-/- mouse can be reduced or partially reversed. Serum amyloid beta levels after systemic administration show accumulation of amyloid beta in the periphery and suggest removal of retinal amyloid beta deposition by a peripheral sink mechanism consistent with the proposed mechanism of this agent. The data support this therapeutic approach in humans.

Keywords: age-related macular degeneration • retina • drusen 
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