Abstract

Objective: Animal models are the silent scouts that help to understand the complex biological processes and gather data that aid our understanding of how organisms function. Various animal models are being sacrificed to assess the impact of toxic chemicals. Mortality calculations should be minimised and much data should be collected on the basis of clinical signs that can contribute to identifying robust humane endpoints linked to mortality. This study was designed to calculate the lowest possible dose of PbAc (lead acetate), a neurotoxicant, that can have a toxicological impact on the zebrafish retina and to minimise animal usage. Dose and time-dependent changes were observed in the zebrafish retina following PbAc exposure with zero mortality. Vision and visual behaviour response are the foremost indicators that can be recorded to mark the risk assessment of any chemical. Therefore, the present study aims at dose and time response to find the lowest dose of PbAc affecting the zebrafish retina and its visual behaviour.

Materials and methods: Zebrafish were treated for 3 weeks with four concentrations of 0.04, 0.06, 0.08, and 0.1 mg/L of PbAc for a dose-response study. Then for the time response study, two doses 0.08 and 0.1 mg/L were selected and zebrafish were exposed to those concentrations for 2 and 4 weeks.

Results: The results of qualitative and quantitative analyses of retinal histology showed that 15 days of treatment with 0.08 mg/L concentration can cause appropriate damage to the photoreceptor layer. At the ultrastructural level, it was further observed that PbAc induces damage to the photoreceptors, especially the rod cells. Escape response sbehaviour showed a significant decrease in visual response to changing contrasts in an increasing dose-dependent manner.

Conclusion: In conclusion, it has been shown that 15 days treatment with 0.08 mg/L lead acetate induce retinal degeneration in zebrafish without causing any mortality.

摘要

客观的：动物模型是无声的侦察员，有助于了解复杂的生物过程并收集有助于我们了解生物体如何运作的数据。正在牺牲各种动物模型来评估有毒化学物质的影响。应尽量减少死亡率计算，并应根据有助于确定与死亡率相关的稳健人道终点的临床症状收集大量数据。本研究旨在计算可能对斑马鱼视网膜产生毒理学影响的神经毒物 PbAc（醋酸铅）的最低剂量，并尽量减少动物的使用。在 PbAc 暴露后，斑马鱼视网膜中观察到剂量和时间依赖性变化，死亡率为零。视觉和视觉行为反应是最重要的指标，可以记录以标记任何化学品的风险评估。因此，本研究旨在研究剂量和时间响应，以找到影响斑马鱼视网膜及其视觉行为的最低剂量的 PbAc。

材料和方法：斑马鱼用 0.04、0.06、0.08 和 0.1 mg/L 四种浓度的 PbAc 处理 3 周，用于剂量反应研究。然后对于时间响应研究，选择了 0.08 和 0.1 mg/L 两种剂量，斑马鱼在这些浓度下暴露 2 周和 4 周。

结果：视网膜组织学定性定量分析结果表明，0.08mg/L浓度治疗15天可对感光层造成适当损伤。在超微结构水平上，进一步观察到 PbAc 会导致光感受器受损，尤其是视杆细胞。逃避反应行为显示，视觉反应以剂量依赖性方式对变化的对比度显着降低。

结论：总之，已表明用 0.08 mg/L 醋酸铅处理 15 天可诱导斑马鱼视网膜变性，而不会导致任何死亡。