Todd Douglas W, Philip Rohit C, Niihori Maki, Ringle Ryan A, Coyle Kelsey R, Zehri Sobia F, Zabala Leanne, Mudery Jordan A, Francis Ross H, Rodriguez Jeffrey J, Jacob Abraham
1 Department of Electrical and Computer Engineering, The University of Arizona , Tucson, Arizona.
2 Department of Otolaryngology, The University of Arizona , Tucson, Arizona.
Zebrafish. 2017 Aug;14(4):331-342. doi: 10.1089/zeb.2016.1412. Epub 2017 May 18.
Zebrafish animal models lend themselves to behavioral assays that can facilitate rapid screening of ototoxic, otoprotective, and otoregenerative drugs. Structurally similar to human inner ear hair cells, the mechanosensory hair cells on their lateral line allow the zebrafish to sense water flow and orient head-to-current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby establishing itself as an excellent biomarker for anatomic damage to lateral line hair cells. Building on work by our group and others, we have built a new, fully automated high-throughput behavioral assay system that uses automated image analysis techniques to quantify rheotaxis behavior. This novel system consists of a custom-designed swimming apparatus and imaging system consisting of network-controlled Raspberry Pi microcomputers capturing infrared video. Automated analysis techniques detect individual zebrafish, compute their orientation, and quantify the rheotaxis behavior of a zebrafish test population, producing a powerful, high-throughput behavioral assay. Using our fully automated biological assay to test a standardized ototoxic dose of cisplatin against varying doses of compounds that protect or regenerate hair cells may facilitate rapid translation of candidate drugs into preclinical mammalian models of hearing loss.
斑马鱼动物模型适用于行为分析，有助于快速筛选耳毒性、耳保护性和耳再生性药物。斑马鱼侧线的机械感觉毛细胞在结构上与人类内耳毛细胞相似，使斑马鱼能够感知水流，并在一种称为趋流性的行为中使头部朝向水流方向。随着耳毒素顺铂暴露量的增加，这种趋流性行为会以剂量依赖的方式恶化，从而成为侧线毛细胞解剖损伤的优秀生物标志物。在我们团队和其他团队工作的基础上，我们构建了一个全新的、全自动的高通量行为分析系统，该系统使用自动图像分析技术来量化趋流性行为。这个新颖的系统由一个定制设计的游泳装置和成像系统组成，成像系统由网络控制的树莓派微型计算机组成，用于捕捉红外视频。自动分析技术可检测单个斑马鱼，计算它们的方向，并量化斑马鱼测试群体的趋流性行为，从而产生一个强大的高通量行为分析。使用我们的全自动生物学分析方法，针对不同剂量的保护或再生毛细胞的化合物，测试标准化剂量的耳毒性顺铂，可能有助于将候选药物快速转化为听力损失的临床前哺乳动物模型。
