Visual impairment affects 253 million people worldwide and new approaches for prevention and treatment are urgently needed. While small molecules with potential beneficial effects can be examined in various model systems, the in vivo evaluation of visual function remains a challenge. The current study introduces a novel imaging system for measuring visually-guided behaviors in larval zebrafish. The imaging system is the first to image four 96-well plates with a single camera for automated measurements of activity in a 384-well format. In addition, it is the first system to project moving visual stimuli and analyze the optomotor response in the wells of a 96-well plate. We found that activity is affected by tricaine, diazepam and flumazenil. Surprisingly, diazepam treatments induce a loss of visual responses, at concentrations that do not affect activity or induce hyperactivity. Overall, our studies show that the developed imaging system is suitable for automated measurements of vertebrate vision in a high-throughput format.
2,2′,3,5′,6-Pentachlorobiphenyl (PCB-95) is an environmental neurotoxicant. There is accumulated evidence that some neurotoxic effects of PCB-95 are caused by increased spontaneous Ca 2+ oscillations in neurons resulting from modifying ryanodine receptors (RyR) in calcium-releasing channels. However, there are large gaps in explaining brain and other developmental malformations on embryonic PCB-95 exposure. In the present study, we address those deficiencies by studying the toxic effects of PCB-95 using zebrafish as an ontogenetic model. To characterize these effects, zebrafish embryos with intact chorions were exposed to 4 different concentrations of PCB-95 (0.25, 0.5, 0.75, and 1 ppm) for 3 consecutive days. The controls were maintained in 0.5 × E2 medium or egg water and in 0.1% (v/v) dimethyl sulfoxide (DMSO)/0.5 × E2 medium or egg water. PCB-95-treated groups showed dose-dependent decreases in survival and hatching rates, with increased rates of developmental malformations when compared to controls. These include morphological malformations, brain cell necrosis, and smaller eye sizes at 5 d post fertilization. These data suggest potential mechanisms underlying the abnormal behavior observed in a visual stimulus assay. The present study provides insight into PCB-95induced developmental toxicity and supports the use of the zebrafish model in understanding the effects of PCB-95 exposure. Environ Toxicol Chem 2020;39:162-170. © 2019 SETAC The Tg(elavl3:EGFP) line, maintained at Brown University, expresses enhanced green fluorescent protein and was utilized wileyonlinelibrary.com/ETC © 2019 SETAC Embryonic PCB-95 exposure and developmental malformations-Environmental Toxicology and Chemistry, 2020;39:162-170 Zhang XQ, Yang L, Zhang M, Guo X, Chi X. 2015. PCB1254 exposure contributes to the abnormalities of optomotor responses and influence of the photoreceptor cell development in zebrafish larvae. Ecotoxicol Environ Saf 118:133-138.
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