A Targeted Inhibitor of the Complement Alternative Pathway Reduces RPE Injury and Angiogenesis in Models of Age-Related Macular Degeneration

  • Bärbel Rohrer
  • Qin Long
  • Beth Coughlin
  • Brandon Renner
  • Yuxiang Huang
  • Kannan Kunchithapautham
  • Viviana P. Ferreira
  • Michael K. Pangburn
  • Gary S. Gilkeson
  • Joshua M. Thurman
  • Stephen Tomlinson
  • V. Michael Holers
Conference paper

DOI: 10.1007/978-1-4419-5635-4_10

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 703)
Cite this paper as:
Rohrer B. et al. (2010) A Targeted Inhibitor of the Complement Alternative Pathway Reduces RPE Injury and Angiogenesis in Models of Age-Related Macular Degeneration. In: Lambris J., Adamis A. (eds) Inflammation and Retinal Disease: Complement Biology and Pathology. Advances in Experimental Medicine and Biology, vol 703. Springer, New York, NY

Abstract

Genetic variations in complement factor H (fH), an inhibitor of the complement alternative pathway (CAP), and oxidative stress are associated with age-related macular degeneration (AMD). Recently, novel complement therapeutics have been created with the capacity to be “targeted” to sites of complement activation. One example is our recombinant form of fH, CR2-fH, which consists of the N-terminus of mouse fH that contains the CAP-inhibitory domain, linked to a complement receptor 2 (CR2) targeting fragment that binds complement activation products. CR2-fH was investigated in vivo in the mouse model of choroidal neovascularization (CNV) and in vitro in oxidatively stressed RPE cell monolayers. RPE deterioration and CNV development were found to require CAP activation, and specific CAP inhibition by CR2-fH reduced the loss of RPE integrity and angiogenesis in CNV. In both the in vivo and in vitro paradigm of RPE damage, a model requiring molecular events known to be involved in AMD, complement-dependent VEGF production, was confirmed. These data may open new avenues for AMD treatment strategies.

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Bärbel Rohrer
    • 1
    • 2
  • Qin Long
  • Beth Coughlin
  • Brandon Renner
  • Yuxiang Huang
  • Kannan Kunchithapautham
  • Viviana P. Ferreira
  • Michael K. Pangburn
  • Gary S. Gilkeson
  • Joshua M. Thurman
  • Stephen Tomlinson
  • V. Michael Holers
  1. 1.Department of OphthalmologyMedical University of South CarolinaCharlestonUSA
  2. 2.Department of NeuroscienceMedical University of South CarolinaCharlestonUSA

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