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

Abstract

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.

Effects of Excess Iron on the Retina: Insights From Clinical Cases and Animal Models of Iron Disorders

“…The characterization of retinal iron content through histochemical approaches showed a heterogeneous distribution, with iron largely found at the choroid, RPE and the photoreceptors layer (Yefimova et al, 2000;Song and Dunaief, 2013). Similarly, iron colocalization at the RPE, choroid and to a lesser degree at the neural retain was confirmed using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) which is a sensitive technique that offers a fast and precise spatially resolved measurement of elements in situ at trace and ultra-trace levels (Pamphlett et al, 2020).…”

Mercury is present in neurons and oligodendrocytes in regions of the brain affected by Parkinson’s disease and co-localises with Lewy bodies

“…( 5 ) Both retinal thinning on optical coherence tomography [ 70 – 72 ] and retinal pathology [ 73 ] have been noted in people with PD. This may relate to mercury being found commonly in the human retinal pigment epithelium and choriocapillaris [ 74 ], as well as mercury being present in retinal ganglion cells, pigment epithelium and endothelial cells of mercury-exposed mice [ 75 ] and primates [ 76 ].…”

Soluble curcumin ameliorates motility, adhesiveness and abrogate parthanatos in cadmium-exposed retinal pigment epithelial cells

“…There is limited data on Cd toxicity effects in the retina. The recent findings on heavy metal content in the human retina have shown that Cd is one of the prior candidates to be an inducer of retinal pathogenesis in the age-related macular degeneration (AMD) (Pamphlett et al, 2020). Oxidative stress and apoptosis were confirmed as undoubted Cd-caused abnormalities in retinal cells (Kalariya et al, 2009;Kletner 2012).…”

“…The vision is one of the most critical sensory functions of mammals. Recent findings on heavy metal content in the human retina have shown that Cd is one of prior candidates to be an inducer of retinal pathogenesis of age-related macular degeneration (Pamphlett et al, 2020). Furthermore, the retinal cells accumulate Cd (Wills et al, 2009).…”