Methylmercury Targets Photoreceptor Outer Segments

Abstract

Human populations experience widespread low level exposure to organometallic methylmercury compounds through consumption of fish and other seafood. At higher levels, methylmercury compounds specifically target nervous systems, and among the many effects of their exposure are visual disturbances, including blindness, which previously were thought to be due to methylmercury-induced damage to the visual cortex. Here, we employ high-resolution X-ray fluorescence imaging using beam sizes of 500 × 500 and 250 × 250 nm(2) to investigate the localization of mercury at unprecedented resolution in sections of zebrafish larvae ( Danio rerio ), a model developing vertebrate. We demonstrate that methylmercury specifically targets the outer segments of photoreceptor cells in both the retina and pineal gland. Methylmercury distribution in both tissues was correlated with that of sulfur, which, together with methylmercury's affinity for thiolate donors, suggests involvement of protein cysteine residues in methylmercury binding. In contrast, in the lens, the mercury distribution was different from that of sulfur, with methylmercury specifically accumulating in the secondary fiber cells immediately underlying the lens epithelial cells rather than in the lens epithelial cells themselves. Since methylmercury targets two main eye tissues (lens and photoreceptors) that are directly involved in visual perception, it now seems likely that the visual disruption associated with methylmercury exposure in higher animals including humans may arise from direct damage to photoreceptors, in addition to injury of the visual cortex.

Phenylthiourea alters toxicity of mercury compounds in zebrafish larvae

“…In these previous studies, the highest mercury concentrations in zebrafish exposed to mercuric chloride were found in the olfactory epithelial cells [7]. In contrast, methylmercury chloride preferentially targeted the developing lens [5][6][7][8]. While zebrafish exposed to mercuric chloride accumulated mercury in the ventricular region of the brain, zebrafish exposed to methylmercury chloride accumulated mercury in the muscle tissue [7].…”

“…6 shows zebrafish head sections from larvae exposed to 0.2 μM CH 3 HgCl in absence and presence of PTU. Cells in the lens and retina are known to be among the primary targets of methylmercury compounds [5][6][7][8]. The differences in pigment levels in the retinal pigmented epithelia in the optical micrographs can be clearly seen as a loss of black coloration in Fig.…”

“…Key characteristics that make the zebrafish an excellent model vertebrate system include nearly transparent embryos, rapid development outside the mother, large egg clutch, and a fully sequenced genome [2]. As a model vertebrate system for studying the development of the embryo, researchers have used zebrafish to explore metal toxicity [2][3][4][5][6][7][8] as well as various human diseases [1,9].…”

Fish eyes and brain as primary targets for mercury accumulation — A new insight on environmental risk assessment

“…The fish eye has a wide surface area in continuous contact with the external medium and thus could be a relevant uptake route of Hg. Exposure of zebrafish larvae to waterborne MeHg revealed that this metal form was preferentially accumulated in the eyes, specifically in the outer layer of the lens (Korbas et al, 2013). Interestingly, MeHg levels in the lens increased even after exposure, indicating that MeHg is accumulated in this eye component also through redistribution from other tissues (Korbas et al, 2013).…”

“…These results clearly show that Hg targets the eyes and particularly the lens. The direct MeHg action on eye sensory cells may be partly responsible for visual disturbances (Korbas et al, 2008(Korbas et al, , 2013. As a result of the unique morphology and stability of eye lens over the organism's life, it has been suggested that lens could potentially offer a historical record of Hg exposures affecting fish throughout its lifetime (Korbas et al, 2008).…”