Universität zu Köln

Smailhodzic, Dzenita, van Asten, Freekje ORCID: 0000-0002-8141-4234, Blom, Anna M., Mohlin, Frida C., den Hollander, Anneke I., van de Ven, Johannes P. H., van Huet, Ramon A. C., Groenewoud, Joannes M. M., Tian, Yuan, Berendschot, Tos T. J. M., Lechanteur, Yara T. E., Fauser, Sascha, de Bruijn, Chris, Daha, Mohamed R., van der Wilt, Gert Jan, Hoyng, Carel B. and Klevering, B. Jeroen (2014). Zinc Supplementation Inhibits Complement Activation in Age-Related Macular Degeneration. PLoS One, 9 (11). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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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<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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Smailhodzic, Dzenita UNSPECIFIED UNSPECIFIED UNSPECIFIED van Asten, Freekje UNSPECIFIED orcid.org/0000-0002-8141-4234 UNSPECIFIED Blom, Anna M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mohlin, Frida C. UNSPECIFIED UNSPECIFIED UNSPECIFIED den Hollander, Anneke I. UNSPECIFIED UNSPECIFIED UNSPECIFIED van de Ven, Johannes P. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Huet, Ramon A. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Groenewoud, Joannes M. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tian, Yuan UNSPECIFIED UNSPECIFIED UNSPECIFIED Berendschot, Tos T. J. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lechanteur, Yara T. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED de Bruijn, Chris UNSPECIFIED UNSPECIFIED UNSPECIFIED Daha, Mohamed R. UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Wilt, Gert Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyng, Carel B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klevering, B. Jeroen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-423373
DOI:	10.1371/journal.pone.0112682
Journal or Publication Title:	PLoS One
Volume:	9
Number:	11
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FACTOR-H POLYMORPHISM; BLUE MOUNTAINS EYE; DIETARY ANTIOXIDANTS; CLINICAL-TRIAL; RISK ALLELES; SYSTEM; PREVALENCE; CFH; RANIBIZUMAB; MACULOPATHY Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42337