Methylmercury-induced visual deficits involve loss of GABAergic cells in the zebrafish embryo retina.

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.