Surgery-free video-oculography in mouse models: enabling quantitative and short-interval longitudinal assessment of vestibular function

Xiaojie Yang; Shiyue Zhou; Jiaojiao Wu; Qun Liao; Changquan Wang; Minghua Liu; Lei Qu; Yuan Zhang; Cheng Cheng; Renjie Chai; Kun Zhang; Xiaojie Yu; Pingbo Huang; Lian Liu; Wei Xiong; Shi Chen; Fangyi Chen

doi:10.1016/j.neulet.2018.12.036

Surgery-free video-oculography in mouse models: enabling quantitative and short-interval longitudinal assessment of vestibular function

Neurosci Lett. 2019 Mar 23:696:212-218. doi: 10.1016/j.neulet.2018.12.036. Epub 2018 Dec 28.

Authors

Xiaojie Yang¹, Shiyue Zhou², Jiaojiao Wu³, Qun Liao⁴, Changquan Wang⁵, Minghua Liu⁶, Lei Qu⁷, Yuan Zhang⁸, Cheng Cheng⁹, Renjie Chai¹⁰, Kun Zhang¹¹, Xiaojie Yu¹², Pingbo Huang¹³, Lian Liu¹⁴, Wei Xiong¹⁵, Shi Chen¹⁶, Fangyi Chen¹⁷

Affiliations

¹ Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430072, China. Electronic address: yangxj3@sustc.edu.cn.
² Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China. Electronic address: zhousy@mail.sustc.edu.cn.
³ Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China. Electronic address: wujj1913@mails.jlu.edu.cn.
⁴ Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China. Electronic address: qunliao_0902@163.com.
⁵ Institute of Microelectronics of Chinese Academy of Sciences, Beijing 100029, China. Electronic address: wangchangquan@ime.ac.cn.
⁶ Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China. Electronic address: liumh@sustc.edu.cn.
⁷ Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Department of Biomedical Engineering, Hebei University of Technology, Tianjin 300130, China. Electronic address: qulei21@163.com.
⁸ Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu 210096, China. Electronic address: 230179765@seu.edu.cn.
⁹ Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu 210096, China; Research Institute of Otolaryngology, Nanjing, Jiangsu 210008, China; Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu 210008, China. Electronic address: 230159248@seu.edu.cn.
¹⁰ Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu 210096, China; Research Institute of Otolaryngology, Nanjing, Jiangsu 210008, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China; Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, Jiangsu 211189, China. Electronic address: renjiec@seu.edu.cn.
¹¹ Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China. Electronic address: zhangk@mail.sustc.edu.cn.
¹² Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China. Electronic address: xyuaq@ust.hk.
¹³ Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China; Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Hong Kong, China; State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China. Electronic address: bohuangp@ust.hk.
¹⁴ School of Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China. Electronic address: liulian15@mails.tsinghua.edu.cn.
¹⁵ School of Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China. Electronic address: wei_xiong@tsinghua.edu.cn.
¹⁶ Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430072, China. Electronic address: shichen@whu.edu.cn.
¹⁷ Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China. Electronic address: chenfy@sustc.edu.cn.

PMID: 30597229
DOI: 10.1016/j.neulet.2018.12.036

Abstract

Vestibulo-ocular reflex (VOR) responding to acceleration stimuli is originated from the vestibular apparatuses and thus widely used as an in vivo indicator of the vestibular function. We have developed a vestibular function testing (VFT) system that allows to evaluate VOR response with improved efficiency. The previously required surgical procedure has been avoided by using a newly designed animal-immobility setup. The efficacy of our VFT system was demonstrated on the mice with vestibular abnormalities caused by either genetic mutations (Lhfpl5^-/- or Cdh23^-/-) or applied vestibulotoxicant (3,3'-iminodipropionitrile, IDPN). Daily longitudinal inspection of the VOR response in the IDPN-administered mice gives the first VOR-based daily-progression profile of the vestibular impairment. The capability of VOR in quantifying the severity of toxicant-induced vestibular deficits has been also demonstrated. The acquired VOR-measurement results were validated against the corresponding behavioral-test results. Further validation against immunofluorescence microscopy was applied to the VOR data obtained from the IDPN-administered mice. We conclude that the improved efficiency of our surgery-free VFT system, firstly, enables the characterization of VOR temporal dynamics and quantification of vestibular-impairment severity that may reveal useful information in toxicological and/or pharmaceutical studies; and, secondly, confers our system promising potential to serve as a high-throughput screener for identifying genes and drugs that affect vestibular function.

Keywords: 3,3′-iminodipropionitrile (IDPN); Behavioral assay; Genetic screen; Mouse model; Ototoxicity; Vestibular function; Vestibulo-ocular reflex (VOR); Video-oculography (VOG).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cadherins / metabolism
Disease Models, Animal
Eye Movements / physiology*
Mice, Transgenic
Reflex, Vestibulo-Ocular / physiology*
Rotation
Vestibular Diseases / physiopathology*
Vestibular Function Tests
Vestibule, Labyrinth / physiology*

Substances

Cadherins
Cdh23 protein, mouse