Methylmercury Targets Photoreceptor Outer Segments

• Published in: ACS chemical biology Vol. 8; no. 10; pp. 2256 - 2263
• Main Authors: Korbas, Malgorzata, Lai, Barry, Vogt, Stefan, Gleber, Sophie-Charlotte, Karunakaran, Chithra, Pickering, Ingrid J, Krone, Patrick H, George, Graham N
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18-10-2013
• Subjects: Animals; Disease Models, Animal; Drug Delivery Systems; Environmental Pollutants - pharmacology; Humans; Methylmercury Compounds - pharmacology; Photoreceptor Cells - drug effects; Pineal Gland - drug effects; Retina - drug effects; Spectrometry, X-Ray Emission; Zebrafish
• ISSN: 1554-8929; 1554-8937
• DOI: 10.1021/cb4004805

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 nm2 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.