Wang Jinghan, Guo Shaojuan, Yang Lixin
State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, 100012 Beijing, China.
State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, 100012 Beijing, China.
Sci Total Environ. 2025 Jan 10;959:178329. doi: 10.1016/j.scitotenv.2024.178329. Epub 2025 Jan 4.
Methylmercury (MeHg) is a neurotoxicant with adverse effects on visual systems from fish to man. Clinical signs of visual deficits including color-vision alterations, visual field constriction and blindness have been frequently identified in patients and affected animals following acute and chronic exposure to MeHg. However, it is still unclear whether MeHg causes developmental defects in the eye. We performed here an experimental study to analyze retinal cells expressing gamma-aminobutyric acid (GABA) of MeHg-exposed zebrafish embryos and combined this with a deep RNA-seq analysis. Exposure of zebrafish embryos to MeHg (10-30 μg/L) from 4 to 96 h post fertilization (hpf) resulted in significantly decreased number of GABAergic neurons located in the ganglion cells layer (GCL) and inner nuclear layer (INL). Twenty μg MeHg/L abolished the color preference characterized in larval zebrafish aged 5 days post fertilization (dpf), and impaired optomotor response (OMR) in larval zebrafish at 6 dpf. The genes playing a role in retinal cell redox homeostasis, steroid hormone and folate biosynthesis, lysosome activity and necroptosis were enriched in MeHg-treated eyes. The expression patterns of genes encoding opsin and genes involved in phototransduction were altered in the eye by MeHg. Our experimental findings show that MeHg disturbs the retinal cells development by interfering with the cell differentiation and cellular homeostasis, which in turn may lead to visual deficits in the larval zebrafish.
甲基汞（MeHg）是一种神经毒素，对从鱼类到人类的视觉系统均有不良影响。在急性和慢性接触MeHg后的患者和受影响动物中，经常发现视觉缺陷的临床症状，包括色觉改变、视野缩小和失明。然而，MeHg是否会导致眼睛发育缺陷仍不清楚。我们在此进行了一项实验研究，以分析暴露于MeHg的斑马鱼胚胎中表达γ-氨基丁酸（GABA）的视网膜细胞，并将其与深度RNA测序分析相结合。在受精后4至96小时（hpf）将斑马鱼胚胎暴露于MeHg（10-30μg/L），导致位于神经节细胞层（GCL）和内核层（INL）的GABA能神经元数量显著减少。20μg MeHg/L消除了受精后5天（dpf）的幼体斑马鱼所具有的颜色偏好，并损害了6 dpf幼体斑马鱼的视动反应（OMR）。在MeHg处理的眼睛中，参与视网膜细胞氧化还原稳态、类固醇激素和叶酸生物合成、溶酶体活性和坏死性凋亡的基因富集。MeHg改变了眼睛中编码视蛋白的基因和参与光转导的基因的表达模式。我们的实验结果表明，MeHg通过干扰细胞分化和细胞内稳态来扰乱视网膜细胞发育，进而可能导致幼体斑马鱼出现视觉缺陷。
