School of Marine Sciences, University of Maine, Orono, ME, USA.
J Appl Toxicol. 2019 Jun;39(6):824-831. doi: 10.1002/jat.3770. Epub 2019 Jan 22.
Arsenic is a metalloid that contaminates drinking water supplies worldwide. Owing to concerns for human health, the World Health Organization and the US Environmental Protection Agency have established a safe level in drinking water of ≤10 ppb. Recently, arsenic exposure has also been linked to lower IQ values in children. The effect of arsenic on neurogenesis, specifically eye development, has not been widely explored. This study aimed to examine the effect of environmentally relevant concentrations of arsenic on early eye development by morphological and molecular analysis. The zebrafish, Danio rerio, was chosen to model the impact of arsenic on retinogenesis because of similarities to human eye development. Arsenic exposure to zebrafish embryos resulted in a significant increase in eye diameter at 14 days postfertilization. This was coupled with a trend in thinning of the retinal pigmented epithelium (RPE) layer in embryos exposed to 500 ppb arsenic. Reverse transcription-quantitative polymerase chain reaction analysis of genes associated with eye development revealed differential expression of Pax6a, Pax2a, Ngn1, Sox2 and Shha relative to control. Pax6a, Pax2a and Sox2 are important in the formation of the RPE. Proper formation of the RPE is necessary for growth of the sclera, which, in turn, is responsible for maintaining the shape of the eye. This could potentially be explained by the disruption of gene expression under arsenic exposure during critical time points in early eye development. These results provide insight into the effects arsenic may be having on early eye development in children exposed to contaminated drinking water supplies.
砷是一种类金属，污染了全世界的饮用水供应。由于对人类健康的担忧，世界卫生组织和美国环境保护署已经将饮用水中的安全水平设定为≤10 ppb。最近，砷暴露也与儿童智商降低有关。砷对神经发生的影响，特别是眼睛发育的影响，尚未得到广泛探讨。本研究旨在通过形态和分子分析来研究环境相关浓度的砷对早期眼睛发育的影响。选择斑马鱼（Danio rerio）来模拟砷对视网膜发生的影响，因为它与人眼发育相似。胚胎暴露于砷会导致受精后 14 天眼睛直径显著增加。这与暴露于 500 ppb 砷的胚胎中视网膜色素上皮（RPE）层变薄的趋势有关。与对照相比，与眼睛发育相关的基因的逆转录定量聚合酶链反应分析显示 Pax6a、Pax2a、Ngn1、Sox2 和 Shha 的表达存在差异。Pax6a、Pax2a 和 Sox2 对于 RPE 的形成很重要。RPE 的正确形成对于巩膜的生长是必要的，巩膜反过来负责维持眼睛的形状。这可能是由于在早期眼睛发育的关键时间点暴露于砷时基因表达的中断。这些结果提供了有关接触受污染饮用水的儿童早期眼睛发育中砷可能产生的影响的见解。
