Zinc supplementation inhibits complement activation in age-related macular degeneration.
<h4>Unlabelled</h4>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...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0112682&type=printable |
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| author | 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 |
| author_facet | 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 |
| author_sort | Dzenita Smailhodzic |
| collection | DOAJ |
| description | <h4>Unlabelled</h4>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.<h4>Trial registration</h4>The Netherlands National Trial Register NTR2605. |
| format | Article |
| id | doaj-art-e0071239818d40fb8f9a03a69f7715c0 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-e0071239818d40fb8f9a03a69f7715c02025-08-20T02:20:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11268210.1371/journal.pone.0112682Zinc supplementation inhibits complement activation in age-related macular degeneration.Dzenita SmailhodzicFreekje van AstenAnna M BlomFrida C MohlinAnneke I den HollanderJohannes P H van de VenRamon A C van HuetJoannes M M GroenewoudYuan TianTos T J M BerendschotYara T E LechanteurSascha FauserChris de BruijnMohamed R DahaGert Jan van der WiltCarel B HoyngB Jeroen Klevering<h4>Unlabelled</h4>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.<h4>Trial registration</h4>The Netherlands National Trial Register NTR2605.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0112682&type=printable |
| spellingShingle | 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 Zinc supplementation inhibits complement activation in age-related macular degeneration. PLoS ONE |
| title | Zinc supplementation inhibits complement activation in age-related macular degeneration. |
| title_full | Zinc supplementation inhibits complement activation in age-related macular degeneration. |
| title_fullStr | Zinc supplementation inhibits complement activation in age-related macular degeneration. |
| title_full_unstemmed | Zinc supplementation inhibits complement activation in age-related macular degeneration. |
| title_short | Zinc supplementation inhibits complement activation in age-related macular degeneration. |
| title_sort | zinc supplementation inhibits complement activation in age related macular degeneration |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0112682&type=printable |
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