PLoS ONE (Jan 2014)

Zinc supplementation inhibits complement activation in age-related macular degeneration.

  • Dzenita Smailhodzic,
  • Freekje van Asten,
  • Anna M Blom,
  • Frida C Mohlin,
  • Anneke I den Hollander,
  • Johannes P H van de Ven,
  • Ramon A C van Huet,
  • Joannes M M Groenewoud,
  • Yuan Tian,
  • Tos T J M Berendschot,
  • Yara T E Lechanteur,
  • Sascha Fauser,
  • Chris de Bruijn,
  • Mohamed R Daha,
  • Gert Jan van der Wilt,
  • Carel B Hoyng,
  • B Jeroen Klevering

DOI
https://doi.org/10.1371/journal.pone.0112682
Journal volume & issue
Vol. 9, no. 11
p. e112682

Abstract

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UnlabelledAge-related macular degeneration (AMD) is the leading cause of blindness in the Western world. AMD is a multifactorial disorder but complement-mediated inflammation at the level of the retina plays a pivotal role. Oral zinc supplementation can reduce the progression of AMD but the precise mechanism of this protective effect is as yet unclear. We investigated whether zinc supplementation directly affects the degree of complement activation in AMD and whether there is a relation between serum complement catabolism during zinc administration and the complement factor H (CFH) gene or the Age-Related Maculopathy susceptibility 2 (ARMS2) genotype. In this open-label clinical study, 72 randomly selected AMD patients in various stages of AMD received a daily supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months. Serum complement catabolism-defined as the C3d/C3 ratio-was measured at baseline, throughout the three months of supplementation and after discontinuation of zinc administration. Additionally, downstream inhibition of complement catabolism was evaluated by measurement of anaphylatoxin C5a. Furthermore, we investigated the effect of zinc on complement activation in vitro. AMD patients with high levels of complement catabolism at baseline exhibited a steeper decline in serum complement activation (pTrial registrationThe Netherlands National Trial Register NTR2605.