Systemic complement activation in age-related macular degeneration

Hendrik P.N. Scholl, Peter Charbel Issa, Maja Walier, Stefanie Janzer, Beatrix Pollok-Kopp, Florian Börncke, Lars G. Fritsche, Ngaihang V. Chong, Rolf Fimmers, Thomas Wienker, Frank G. Holz, Bernhard H.F. Weber, Martin Oppermann

Research output: Contribution to journalArticlepeer-review

266 Scopus citations


Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood, plasm were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, Ga, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor b were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated witt AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<001), were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the control's and AMD patients' group, the protein markers of complement activation-were correlated with CFH haplotypes. This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing, macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement. pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

Original languageEnglish (US)
Article numbere2593
JournalPloS one
Issue number7
StatePublished - Jul 2 2008
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General


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