Levels of Aqueous Humor Trace Elements in Patients with Non-Exsudative Age-related Macular Degeneration: A Case-control Study

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.

Iron accumulation in Bruch's membrane and melanosomes of donor eyes with age-related macular degeneration

“…Other heavy metals like cadmium and lead have also been linked to ocular neurodegeneration (Kazi et al, 2006) (Junemann et al, 2013). Lead was associated with cataract in men (Schaumberg et al, 2004) and low-tension glaucoma in women (Yuki et al, 2009).…”

On-Set of Cataract and Accumulation of Copper, Lead and Cadmium in Smokers of Karachi, Pakistan

“…Metals present in Cigarette are responsible for producing reactive oxygen species [79,80]. As metals have a long halflife deposition in tissues occur [61] the radicals produced can cause peroxidation of Lipids, biomolecules degradation and breakup of DNA strand [81]. Cumulative damage to mitochondria can occur due to oxidative damage which is important for providing energy and cell survival [82], these metals can directly bind to antioxidant enzymes like Glutathione & increases their inactivated form to get deposited in lens [83].…”

Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

“…The induction of HO-1 expression is the consequence of transcriptional activation of the HO-1 gene by cadmium [35]. In this context, the concentration of aqueous humor cadmium in patients with AMD was reported to be about 1 lmol/L (1 lM) [16]. Importantly, there were no noticeable changes in the expression levels of b-catenin and b-actin proteins over the 24-h treatment with cadmium.…”

“…MITF isoform multiplicity has been evolved to enable RPE to maintain total MITF protein levels, most likely MITF-H. This may provide RPE survival advantage because they are at increased risk for cadmium toxicity due to cumulative lifetime exposure [15,16,21].…”

“…Cadmium, an environmental toxicant, has been implicated in the pathogenesis of various chronic diseases [12,13], including age-related macular degeneration (AMD) [14][15][16] and hearing loss [17,18]. Diet and cigarette smoking are the main sources of cadmium in the general population [19]; the estimated amount of cadmium intake ranges from 10 to 30 lg/day in developed countries.…”