Abstract
Trace elements might play a role in the complex multifactorial pathogenesis of age-related macular degeneration (AMD). The aim of this study was to measure alterations of trace elements levels in aqueous humor of patients with non-exsudative (dry) AMD.For this pilot study, aqueous humor samples were collected from patients undergoing cataract surgery. 12 patients with dry AMD (age 77.9±6.62, female 8, male 4) and 11 patients without AMD (age 66.6±16.7, female 7, male 4) were included. Aqueous levels of cadmium, cobalt, copper, iron, manganese, selenium, and zinc were measured by use of Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS), quality controlled with certified standards.Patients with AMD had significantly higher aqueous humor levels of cadmium (median: 0.70 µmol/L, IQR: 0.40–0.84 vs. 0.06 µmol/L; IQR: 0.01–.018; p = 0.002), cobalt (median: 3.1 µmol/L, IQR: 2.62–3.15 vs. 1.17 µmol/L; IQR: 0.95–1.27; p<0.001), iron (median: 311 µmol/L, IQR: 289–329 vs. 129 µmol/L; IQR: 111–145; p<0.001) and zinc (median: 23.1 µmol/L, IQR: 12.9–32.6 vs. 5.1 µmol/L; IQR: 4.4–9.4; p = 0.020) when compared with patients without AMD. Copper levels were significantly reduced in patients with AMD (median: 16.2 µmol/L, IQR: 11.4–31.3 vs. 49.9 µmol/L; IQR: 32.0–.142.0; p = 0.022) when compared to those without. No significant differences were observed in aqueous humor levels of manganese and selenium between patients with and without AMD. After an adjustment for multiple testing, cadmium, cobalt, copper and iron remained a significant factor in GLM models (adjusted for age and gender of the patients) for AMD.Alterations of trace element levels support the hypothesis that cadmium, cobalt, iron, and copper are involved in the pathogenesis of AMD.
Highlights
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in industrialized countries
A General Linear Model (GLM) with age as covariate and gender and AMD as factors was calculated for each trace element.After an adjustment for multiple testing, AMD was a significant factor in GLM models regarding cadmium, cobalt, copper, and iron
In the present study we observed significantly higher levels of cadmium, cobalt, iron, and zinc, while copper levels were reduced in the aqueous humor of patients diagnosed with AMD when compared with patients without AMD
Summary
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in industrialized countries. The exact etiology of this complex multifactorial disease is unknown, but is believed to involve interaction of genetic and environmental factors [1]. There is some evidence that trace elements might play a role in the pathogenesis of AMD. Iron is a potent generator of reactive oxygen species (ROS), whose generation within mitochondria and lysosomes may promote cell death [2]. Iron has been suggested as a source of oxidants in AMD, as AMD-affected maculas were found to have higher concentrations of iron than healthy agematched maculas [3]. Iron was found in the retinal pigment epithelium (RPE) and Bruch’s membrane in early AMD, geographic atrophy, and exudative AMD
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