Elemental concentrations in Choroid-RPE and retina of human eyes with age-related macular degeneration

Aberami, Seeneevasan; Nikhalashree, Sampath; Bharathselvi, Muthuvel; Biswas, Jyotirmay; Sulochana, K N; Coral, Karunakaran

doi:10.1016/j.exer.2019.107718

Cited by 27 publications

(24 citation statements)

References 26 publications

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“…Previous reports have described toxic metals in the human choriocapillaris as well as in the RPE [ 5 – 7 ], and toxic metals were often detected in the choriocapillaris of our samples. Although the role of the choriocapillaris in AMD is contestable, it remains one of regions suspected to play a role in this disorder [ 24 ].…”

Section: Discussionsupporting

confidence: 49%

“…The RPE is affected early and severely in AMD, and because its many functions protect the neural retina from damage [ 2 ] interest has arisen in finding agents that could injure the RPE. One proposal is that toxic metals from environmental sources accumulate in the RPE over time, until their concentrations reach a tipping point that impairs the function of RPE cells, with subsequent injury to the photoreceptors of the adjacent outer neural retina [ 3 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Toxic metals have previously been detected in the human RPE, choriocapillaris and neural retina [ 3 – 7 ]. In four donors (aged 76–90 years, without clinicopathological details) X-ray microanalysis of 3x3 mm samples of RPE detected iron in melanosomes of all four donors, aluminium in three, and mercury in one [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…In 22 donors of normal eyes (aged 16 to 87 years) inductively coupled plasma-mass spectrometry and atomic absorption spectrophotometry showed that average cadmium levels were high in the RPE in those aged <55 years, and high in the RPE, choriocapillaris and neural retina in those aged 55 years and over [ 6 ]. A comparison of toxic metal levels in 39 control (mean age 83 years) eyes and 51 AMD (mean age 80 years) eyes, using inductively coupled plasma-mass spectrometry, showed that average levels of lead, cadmium, chromium, arsenic and nickel were higher in both the RPE/choriocapillaris and neural retina in the AMD group; in the control group, raised levels of metals were present only occasionally in the RPE/choriocapillaris (nickel in three, cadmium in two, and lead and chromium in one each), while in only one neural retina was nickel high [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…We therefore looked for toxic metals in the normal retina in situ using two techniques, laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), which detects multiple elements simultaneously in tissues, and autometallography which demonstrates intracellular inorganic mercury, silver, and bismuth. These elemental analyses enabled us to assess the presence of toxic metals within the normal aging retina, so that primary metal accumulation (that could predispose to AMD) could be distinguished from the secondary uptake of metals by retinal cells that had been damaged by AMD [ 1 , 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

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The distribution of toxic metals in the human retina and optic nerve head: Implications for age-related macular degeneration

et al. 2020

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Objective Toxic metals are suspected to play a role in the pathogenesis of age-related macular degeneration. However, difficulties in detecting the presence of multiple toxic metals within the intact human retina, and in separating primary metal toxicity from the secondary uptake of metals in damaged tissue, have hindered progress in this field. We therefore looked for the presence of several toxic metals in the posterior segment of normal adult eyes using elemental bioimaging. Methods Paraffin sections of the posterior segment of the eye from seven tissue donors (age range 54–74 years) to an eye bank were examined for toxic metals in situ using laser ablation-inductively coupled plasma-mass spectrometry, a technique that detects multiple elements in tissues, as well as the histochemical technique of autometallography that demonstrates inorganic mercury, silver, and bismuth. No donor had a visual impairment, and no significant retinal abnormalities were seen on post mortem fundoscopy and histology. Results Metals found by laser ablation-inductively coupled plasma-mass spectrometry in the retinal pigment epithelium and choriocapillaris were lead (n = 7), nickel (n = 7), iron (n = 7), cadmium (n = 6), mercury (n = 6), bismuth (n = 5), aluminium (n = 3), and silver (n = 1). In the neural retina, mercury was present in six samples, and iron in one. Metals detected in the optic nerve head were iron (N = 7), mercury (N = 7), nickel (N = 4), and aluminium (N = 1). No gold or chromium was seen. Autometallography demonstrated probable inorganic mercury in the retinal pigment epithelium of one donor. Conclusion Several toxic metals are taken up by the human retina and optic nerve head. Injury to the retinal pigment epithelium from toxic metals could damage the neuroprotective functions of the retinal pigment epithelium and allow toxic metals to enter the outer neural retina. These findings support the hypothesis that accumulations of toxic metals in the retina could contribute to the pathogenesis of age-related macular degeneration.

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Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The distribution of toxic metals in the human retina and optic nerve head: Implications for age-related macular degeneration

et al. 2020

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Elemental mass spectrometry to study metallo-transcriptomic changes during the in vitro degeneration of the retinal pigment epithelium

et al. 2023

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Trace elements play crucial roles in cellular biology. Their improper homeostasis may contribute to the progress of eye diseases, exacerbated during ageing. The retinal pigment epithelium (RPE) is progressively deteriorated during age-related neurodegeneration and metal homeostasis may be compromised. In this study, elemental mass spectrometry (MS) was combined with cellular and molecular biology techniques to identify changes in trace elements during the in vitro degeneration of human RPE cells. Cells were collected at 21, 91, and 133 days and processed for RNA sequencing; Ca, Na, P, Mg, and Cu quantification by flow injection analysis and inductively coupled plasma–MS; and protein analysis by immunocytochemistry. Four-month-old RPE cultures showed depigmentation, impaired barrier function, and antioxidant protection, manifesting signs of epithelial-to-mesenchymal transition. Na and P significantly increased in the cytosol of degenerated RPE cells (from 15 ± 20 to 13495 ± 638 ng·µg−1 and from 30.6 ± 9.5 to 116.8 ± 16.8 ng·µg−1, respectively). Mg decreased in both the cytosol and insoluble fraction of cells (from 2.83 ± 0.40 to 1.58 ± 0.56 ng·µg−1 and from 247.57 ± 11.06 to 30 ± 8 ng·g−1, respectively), while P and Cu decreased in the insoluble fraction after 133 days in culture (from 9471 ± 1249 to 4555 ± 985 ng·µg−1 and from 2251 ± 79 to 1054 ± 235 ng·g−1, respectively), along with changes in metal-dependent antioxidant enzymes and Cu transporters. This RPE model reflected metal homeostatic changes, providing additional perspectives on effects of metal regulation during ageing. Graphical Abstract

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Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions

et al. 2019

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Aging of the microcirculatory network plays a central role in the pathogenesis of a wide range of agerelated diseases, from heart failure to Alzheimer's disease. In the eye, changes in the choroid and choroidal microcirculation (choriocapillaris) also occur with age, and these changes can play a critical role in the pathogenesis of age-related macular degeneration (AMD). In order to develop novel treatments for amelioration of choriocapillaris aging and prevention of AMD, it is essential to understand the cellular and functional changes that occur in the choroid and choriocapillaris during aging. In this review, recent advances in in vivo analysis of choroidal structure and function in AMD patients and patients at risk for AMD are discussed. The pathophysiological roles of fundamental cellular and molecular mechanisms of aging including oxidative GeroScience

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Elemental concentrations in Choroid-RPE and retina of human eyes with age-related macular degeneration

Cited by 27 publications

References 26 publications

The distribution of toxic metals in the human retina and optic nerve head: Implications for age-related macular degeneration

The distribution of toxic metals in the human retina and optic nerve head: Implications for age-related macular degeneration

Elemental mass spectrometry to study metallo-transcriptomic changes during the in vitro degeneration of the retinal pigment epithelium

Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions

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