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

Smailhodzic, Dzenita; van Asten, Freekje; Blom, Anna LU ; Mohlin, Frida LU ; den Hollander, Anneke I; van de Ven, Johannes P H; van Huet, Ramon A C; Groenewoud, Joannes M M; Tian, Yuan and Berendschot, Tos T J M, et al. (2014) In PLoS ONE 9(11).
Abstract
Age-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... (More)
Age-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 (p<0.001) during the three month zinc supplementation period compared to patients with low complement levels. There was no significant association of change in complement catabolism and CFH and ARMS2 genotype. In vitro zinc sulphate directly inhibits complement catabolism in hemolytic assays and membrane attack complex (MAC) deposition on RPE cells. This study provides evidence that daily administration of 50 mg zinc sulphate can inhibit complement catabolism in AMD patients with increased complement activation. This could explain part of the mechanism by which zinc slows AMD progression. (Less)
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PLoS ONE
volume
9
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11
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Public Library of Science
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  • pmid:25393287
  • wos:000347709300085
  • scopus:84911472224
ISSN
1932-6203
DOI
10.1371/journal.pone.0112682
language
English
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yes
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2f4c336c-b30a-447a-ad06-59c354377e6d (old id 4816773)
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http://www.ncbi.nlm.nih.gov/pubmed/25393287?dopt=Abstract
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2014-12-02 16:34:13
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2017-10-01 04:08:05
@article{2f4c336c-b30a-447a-ad06-59c354377e6d,
  abstract     = {Age-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 (p&lt;0.001) during the three month zinc supplementation period compared to patients with low complement levels. There was no significant association of change in complement catabolism and CFH and ARMS2 genotype. In vitro zinc sulphate directly inhibits complement catabolism in hemolytic assays and membrane attack complex (MAC) deposition on RPE cells. This study provides evidence that daily administration of 50 mg zinc sulphate can inhibit complement catabolism in AMD patients with increased complement activation. This could explain part of the mechanism by which zinc slows AMD progression.},
  articleno    = {e112682},
  author       = {Smailhodzic, Dzenita and van Asten, Freekje and Blom, Anna and Mohlin, Frida and den Hollander, Anneke I and van de Ven, Johannes P H and van Huet, Ramon A C and Groenewoud, Joannes M M and Tian, Yuan and Berendschot, Tos T J M and Lechanteur, Yara T E and Fauser, Sascha and de Bruijn, Chris and Daha, Mohamed R and van der Wilt, Gert Jan and Hoyng, Carel B and Klevering, B Jeroen},
  issn         = {1932-6203},
  language     = {eng},
  number       = {11},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Zinc supplementation inhibits complement activation in age-related macular degeneration.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0112682},
  volume       = {9},
  year         = {2014},
}