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

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.