May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Systemic Complement Activation in Patients With Age-Related Macular Degeneration
Author Affiliations & Notes
  • P. Charbel Issa
    University of Bonn, Bonn, Germany
    Department of Ophthalmology,
  • H. P. N. Scholl
    University of Bonn, Bonn, Germany
    Department of Ophthalmology,
  • S. Janzer
    University of Bonn, Bonn, Germany
    Department of Ophthalmology,
  • F. Boernke
    Department of Cellular and Molecular Immunology, University of Goettingen, Goettingen, Germany
  • N. V. Chong
    Oxford Eye Hospital, University of Oxford, Oxford, United Kingdom
  • R. Fimmers
    University of Bonn, Bonn, Germany
    Institute of Medical Biometry, Informatics and Epidemiology,
  • T. Wienker
    University of Bonn, Bonn, Germany
    Institute of Medical Biometry, Informatics and Epidemiology,
  • F. G. Holz
    University of Bonn, Bonn, Germany
    Department of Ophthalmology,
  • B. H. F. Weber
    Institute for Human Genetics, University of Regensburg, Regensburg, Germany
  • M. Oppermann
    Department of Cellular and Molecular Immunology, University of Goettingen, Goettingen, Germany
  • Footnotes
    Commercial Relationships  P. Charbel Issa, None; H.P.N. Scholl, None; S. Janzer, None; F. Boernke, None; N.V. Chong, None; R. Fimmers, None; T. Wienker, None; F.G. Holz, None; B.H.F. Weber, None; M. Oppermann, None.
  • Footnotes
    Support  Pro Retina Foundation Pro-Re/Seed/Issa.1; EU FP6, Integrated Project "EVI-GENORET" (LSHG-CT-2005-512036); DFG Heisenberg Fellowship SCHO 734/2-1; DFG WE 1259/14-3; Ruth and Milton Steinbach Foundation
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1357. doi:
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    • Get Citation

      P. Charbel Issa, H. P. N. Scholl, S. Janzer, F. Boernke, N. V. Chong, R. Fimmers, T. Wienker, F. G. Holz, B. H. F. Weber, M. Oppermann; Systemic Complement Activation in Patients With Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1357.

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

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Abstract

Purpose: : To detect alterations of marker proteins involved in the alternative complement pathway in patients with age-related macular degeneration (AMD).

Methods: : 112 AMD patients and 67 control subjects were analyzed for genetic polymorphisms in the complement factor H (CFH), factor B and complement component C2 (CFB-C2) and complement component C3 genes (see Abstract Scholl et al.). Plasma levels of substrates of the complement system (C3, C4, CFB), markers for acute complement activation (C3a, C5a), markers for chronic complement activation (C3d, Ba, C5b-9) and regulators of the complement system (CFH, factor D) were measured.

Results: : Plasma concentration of CFH did not differ between the AMD patient group and the control group (median AMD, 546 µg/ml [5th, 95th percentiles: 396, 758]; median controls, 515 µg/ml [365, 711]; p=0.21). This was also true for the complement substrates C3 (AMD, 1.12 g/l [0.89, 1.53]; controls, 1.19 g/l [0.85, 1.48]; p=1.0) and C4 (AMD, 0.23 g/l [0.15, 0.38]; controls, 0.24 g/l [0.15, 0.34]; p=1.0). CFB was increased in the AMD population (AMD, 803 µg/ml [497, 1489]; controls, 642 µg/ml [378, 1354]; p=0.02) as was factor D (AMD, 1.27 µg/ml [0.69, 2.30];controls, 0.95 µg/ml [0.50, 1,65]; p < 0.001). The AMD group showed a significant increase of protein markers for acute complement activation, C3a (AMD, 15.5 ng/ml [11.2, 24.1]; controls, 14.3 ng/ml [10.6, 21.2]; p=0.03) and C5a (AMD, 1.85 ng/ml [0.78, 2.66], controls, 1.67 ng/ml [0.66, 2.32]; p=0.04) and for chronic complement activation, C3d (AMD, 55.2 ng/ml [33.7, 94.1]; controls, 46.9 ng/ml [32.2, 68.5]; p<0.001), Ba (AMD, 1.33 µg/ml [0.90, 2.09]; controls, 1.09 µg/ml [0.60, 1.71]; p<0.001) and SC5b-9 (AMD, 188 units [107, 777]; controls, 159 units [90, 710]; p=0.01).

Conclusions: : AMD patients exhibit a systemic alteration of proteins involved in the alternative complement cascade. The strongest effect was observed for factor D, Ba and C3d. This study supports a major role of inflammation in the pathogenesis of AMD, specifically of the alternative complement pathway.

Keywords: age-related macular degeneration • immunomodulation/immunoregulation • genetics 
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