April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Evaluation of Serum Complement Levels in Age-Related Macular Degeneration (amd)
Author Affiliations & Notes
  • D. Smailhodzic
    Ophthalmology, Radboud University Nijmegen Medical Centre Nijmegen, Nijmegen, The Netherlands
  • S. Liakopoulos
    Ophthalmology, University of Cologne, Cologne, Germany
  • B. J. Klevering
    Ophthalmology, Radboud University Nijmegen Medical Centre Nijmegen, Nijmegen, The Netherlands
  • C. J. F. Boon
    Ophthalmology, Radboud University Nijmegen Medical Centre Nijmegen, Nijmegen, The Netherlands
  • B. Kirchhof
    Ophthalmology, University of Cologne, Cologne, Germany
  • M. R. Daha
    Nephrology, Leiden University Medical Center, Leiden, The Netherlands
  • C. C. W. Klaver
    Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands
  • A. I. Den Hollander
    Ophthalmology, Radboud University Nijmegen Medical Centre Nijmegen, Nijmegen, The Netherlands
  • C. B. Hoyng
    Ophthalmology, Radboud University Nijmegen Medical Centre Nijmegen, Nijmegen, The Netherlands
  • Footnotes
    Commercial Relationships  D. Smailhodzic, None; S. Liakopoulos, None; B.J. Klevering, None; C.J.F. Boon, None; B. Kirchhof, None; M.R. Daha, None; C.C.W. Klaver, None; A.I. Den Hollander, None; C.B. Hoyng, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 6201. doi:
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      D. Smailhodzic, S. Liakopoulos, B. J. Klevering, C. J. F. Boon, B. Kirchhof, M. R. Daha, C. C. W. Klaver, A. I. Den Hollander, C. B. Hoyng; Evaluation of Serum Complement Levels in Age-Related Macular Degeneration (amd). Invest. Ophthalmol. Vis. Sci. 2010;51(13):6201.

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

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  • Supplements
Abstract

Purpose: : To measure the concentration of various components of the complement cascade in patients with age-related macular degeneration (AMD) compared to age-matched control individuals. To evaluate the influence of 12 single nucleotide polymorphism (SNP) genotypes on the serum complement levels.

Methods: : Two hundred advanced stage AMD patients and 150 controls of similar age and gender were selected from EUGENDA, a multicentre database for clinical and molecular analysis of AMD. Hemolytic complement assays (AP50, CP50, MBL50), complement components (C3, CFB, CFI and CFH) and activation fragments (C3d, C5a, SC5b-9) were analyzed in serum and plasma. DNA samples were genotyped for 12 SNPs in 9 genes, previously associated with AMD: CFH, CFB, C3, ARMS2, TLR3, TLR4, SERPING1, ABCA4 and APOE. Correlations between complement biomarkers and genotype, age, gender, smoking, and body mass index were evaluated.

Results: : Plasma markers of complement activation fragments (C3d, p<0.0001 and C5a, p<0.0001) were significantly elevated in AMD patients. Interestingly, there was no significant difference in the level of the terminal complex SC5b-9 between AMD and controls (p=0.66). Enzyme precursor factor B was also detectable at higher levels in AMD patients (p=0.0003). Increased activation of the alternative pathway appeared to be the primary cause of the increase in complement levels (p=0.0003). There was no significant difference in the activity of the classical pathway (p=0.56) and the lectin pathway (p=0.25) between AMD patients and controls. The CFH genotype had the most prominent effect on complement activation fragments (C3d and C5a) in AMD patients.

Conclusions: : This study confirms that ongoing low level activation of the alternative pathway of the complement system is associated with AMD.

Keywords: age-related macular degeneration • inflammation • gene screening 
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