Cadmium accumulation in the human retina: Effects of age, gender, and cellular toxicity

Wills, N. K.; Ramanujam, V. M. Sadagopa; Chang, Jeffrey P.; Kalariya, Nilesh; Lewis, J.R.; Weng, Tianxiang; Kuijk, Frederik J.G.M. van

doi:10.1016/j.exer.2007.09.005

Cited by 63 publications

(50 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plasma and retinal levels of cadmium are significantly higher in smokers than non-smokers (Bernhard et al 2006). Cadmium accumulates preferentially in the RPE and choroid (Wills et al 2008) and may contribute to the development of AMD through an increase in reactive oxygen species. Cadmium exposure reduces viability and membrane integrity of cultured RPE cells and this damage was likely oxidative (Wills et al 2008).…”

Section: Cadmium-induced Oxidative Stressmentioning

confidence: 98%

“…Cadmium accumulates preferentially in the RPE and choroid (Wills et al 2008) and may contribute to the development of AMD through an increase in reactive oxygen species. Cadmium exposure reduces viability and membrane integrity of cultured RPE cells and this damage was likely oxidative (Wills et al 2008). Interestingly, cadmium has been found at increased concentrations in the urine of smokers and non-smokers with AMD supporting a role for cadmium in the pathogenesis of AMD (Eric et al 2007).…”

Section: Cadmium-induced Oxidative Stressmentioning

confidence: 99%

See 1 more Smart Citation

The Pathophysiology of Cigarette Smoking and Age-Related Macular Degeneration

Dhubhghaill

Cahill

Campbell

et al. 2009

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is the most common form of visual impairment, in people over 65, in the Western world. AMD is a multifactorial disease with genetic and environmental factors influencing disease progression. Cigarette smoking is the most significant environmental influence with an estimated increase in risk of 2- to 4-fold. Smoke-induced damage in AMD is mediated through direct oxidation, depletion of antioxidant protection, immune system activation and atherosclerotic vascular changes. Moreover, cigarette smoke induces angiogenesis promoting choroidal neovascularisation and progression to neovascular AMD. Further investigation into the effects of cigarette smoke through in vitro and in vivo experimentation will provide a greater insight into the pathogenesis of age-related macular degeneration.

show abstract

Section: Cadmium-induced Oxidative Stressmentioning

confidence: 98%

Section: Cadmium-induced Oxidative Stressmentioning

confidence: 99%

The Pathophysiology of Cigarette Smoking and Age-Related Macular Degeneration

Dhubhghaill

Cahill

Campbell

et al. 2009

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…24, 25 The concentration of Cd 2+ (as well as other heavy metals) rise with age, more so for smokers and old females; 63, 64 Cd 2+ has a physiological half-life of 10-30 years. 65 Since Cd 2+ binds more strongly to human MTs than Zn 2+ , Zn 2+ is released in this process: 31, 67 Electrochemical studies have shown that in human MTs, Cd 2+ substitutes Zn 2+ , releases free Zn 2+ , and gives rise to several complexes that are hard to distinguish in NMR spectra.…”

Section: Biological Implicationsmentioning

confidence: 99%

The building blocks of metallothioneins: heterometallic Zn2+ and Cd2+ clusters from first-principles calculations

Jensen

Rykær

2010

Dalton Trans.

View full text Add to dashboard Cite

Electronic structures of Zn 2+ and Cd 2+ thiolate clusters found in metallothioneins (MT) have been obtained using density functional theory. We have found that the inherent asymmetry of cluster architectures gives rise to seven distinct metal sites. Whereas the non-strained bond lengths of such tetrathiolate complexes are found to be 2.60Å and 2.39Å for Cd-S and Zn-S, in the MT clusters four characteristic terminal and bridging bonds are observed with average lengths 2.55Å (Cd-S t ); 2.35Å (Zn-S t ); 2.62Å (Cd-S b ); and 2.42Å (Zn-S b ). For each stoichiometry of Zn 2+ and Cd 2+ , all possible isomers have been characterized and ranked according to relative free energy and metal ion selectivity. The most stable distribution at low Cd 2+ concentration is computed to be Zn 4 + CdZn 2 , whereas at 2 : 1 Cd 2+ : Zn 2+ concentration, only heteroclusters are thermodynamically stable, explaining experimental data. The presence of two different clusters in MTs must and can be rationalized already in their intrinsic differences. The results indicate that the asymmetry allows for Zn 2+ transfer to various molecular targets having different thresholds for Zn 2+ binding, while maintaining detoxification sites.

show abstract

“…Another heavy metal, iron, may play a role in retinal and macular degeneration, glaucoma, and cataract (He et al, 2007). In vitro experiments carried out in retinal pigment epithelium cells have shown that cadmium can cause disruption of the membrane integrity, alter the cell morphology, and decrease the survival of the cells and could therefore play a role in age-related retinal disease in smokers (Wills et al, 2008). Cobalt toxicity following hip implant has also been reported involving degenerative alterations of the photoreceptor-retinal pigment epithelium complex with coroidal infarction and paracentral scotomas (Ng et al, 2013).…”

Section: Systemic Agents and Ocular Toxicitymentioning

confidence: 99%