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B. Jeroen Klevering, Dzenita Smailhodzic, Anneke Den Hollander, Johannes van de Ven, Joannes Groenewoud, Sacha Fauser, Mohamed Daha, Gert Jan van der Wilt, Carel Hoyng; Zinc supplementation lowers complement overactivation in patients with age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4145.
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Complement-mediated inflammation plays a pivotal role in the pathogenesis of age-related macular degeneration (AMD). Oral zinc administration can reduce the progression of AMD. The purpose of this study was to determine wether zinc supplementation in AMD patients has a direct measurable effect on the complement system, explaining the mechanism through which zinc exerts its protective influence on AMD progression.
In this open-label study, 72 patients in various stages of AMD received a daily supplement of 50 mg zinc sulphate for three months. Serum complement catabolism— defined as the C3d/C3 ratio—was measured at baseline, throughout the three-month of zinc supplementation and after discontinuation of zinc administration. The high-risk genetic variants in CFH Y402H and ARMS2 A69S were determined, and the stage of the disease was assessed in accordance with clinical age-related maculopathy staging.
Serum zinc concentration increased significantly during the supplementation period (p<0.0001) and returned to baseline levels two months after the zinc supplements were discontinued. AMD patients with high levels of complement catabolism at baseline exhibited a steep decline in serum complement activation (p<0.0001) during the 3-month zinc supplementation period. Serum complement catabolism in AMD patients who already had a relatively low C3d/C3 ratio at baseline did not change significantly throughout the study period (Fig. 1). Individuals who were homozygous for the CFH Y402H high-risk genotype had a significantly faster decline in their C3d/C3 ratio (p=0.016). Patients with late-stage AMD in both eyes but no evidence of disease activity had significantly lower levels of serum complement activation than patients with intermediate-stage AMD (p=0.005).
Increased levels of complement catabolism in AMD patients can be lowered towards normal values by daily administration of 50 mg zinc sulphate.
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