Zhao Tong, Xiao Shijie, Liu Wenda, Zhong Jinhao, Sun Binxian, Chen Fangyi
Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China.
Giant Technologies Co., Ltd, Shenzhen, Guangdong, 518055, China.
J Assoc Res Otolaryngol. 2025 Aug 29. doi: 10.1007/s10162-025-01007-x.
In the fields of both vestibular and auditory research, reliable vestibular function tests are essential. However, unlike the auditory function tests, which use standard Auditory Brainstem Response (ABR) equipment, there is no equivalent widely adopted apparatus for vestibular tests. Vestibulo-ocular reflexes (VORs) are the compensatory ocular reflexes that ensure stable vision during head motion. VORs are widely used in clinics to diagnose vestibular deficits. In the research, VORs have been used by various groups to evaluate the mouse vestibular function. However, the effectiveness of VOR tests has not been systematically evaluated with appropriate mouse models, and the lack of commercial equipment hampers its accessibility, confining vestibular testing to a select few labs.
In this study, we developed an integrated and surgery-free instrument system with both angular VOR (aVOR) and off-vertical axis rotation (OVAR) modes for evaluating mouse vestibular function. In addition, the eye rotation calibrations used in this study standardize the data between instruments. To demonstrate its validity and efficacy of the testing equipment, we evaluated four mouse models, including both genders, with peripheral vestibular deficits: 1) mice injected with the vestibulotoxic drug 3,3'-iminodiproprionitrile (IDPN, 2 mg/g and 4 mg/g, 3 male/3 female per group); 2) Critical MET-related mutant mice (Cdh23, 4 male/4 female and TMC1, 6 male/5 female); 3) Vestibular-specific mutant mice (Zpld1, 6 male/6 female, for semicircular canal dysfunction and Otop1, 3 male/2 female, for otoconia deficient); 4) Unilateral vestibular lesion (UVL) mouse model (3 male/3 female per group) where gentamicin was injected into horizontal semicircular canal.
The results showed: 1) Quantification of vestibular deficits can be achieved as a daily routine; 2) Both the horizontal semicircular canal and otolith organs can be assessed, respectively; and 3) The lesion side of UVL can be identified.
These test results reveal the potential of our system as standard equipment for evaluating common vestibular deficits in mice.
在前庭和听觉研究领域，可靠的前庭功能测试至关重要。然而，与使用标准听性脑干反应（ABR）设备的听觉功能测试不同，目前尚无广泛采用的等效前庭测试设备。前庭眼反射（VOR）是在头部运动期间确保视觉稳定的代偿性眼反射。VOR在临床上广泛用于诊断前庭功能缺陷。在研究中，不同研究团队已使用VOR来评估小鼠的前庭功能。然而，VOR测试的有效性尚未通过合适的小鼠模型进行系统评估，并且缺乏商业设备限制了其可及性，使得前庭测试仅局限于少数实验室。
在本研究中，我们开发了一种集成的、无需手术的仪器系统，该系统具有角向VOR（aVOR）和离垂直轴旋转（OVAR）模式，用于评估小鼠前庭功能。此外，本研究中使用的眼动校准使不同仪器之间的数据标准化。为证明测试设备的有效性和效能，我们评估了四种具有外周前庭功能缺陷的小鼠模型，包括不同性别：1）注射前庭毒性药物3,3'-亚氨基二丙腈（IDPN，2mg/g和4mg/g，每组3只雄性/3只雌性）的小鼠；2）关键MET相关突变小鼠（Cdh23，4只雄性/4只雌性和TMC1，6只雄性/5只雌性）；3）前庭特异性突变小鼠（Zpld1，6只雄性/6只雌性，用于半规管功能障碍；Otop1，3只雄性/2只雌性，用于耳石缺乏）；4）单侧前庭损伤（UVL）小鼠模型（每组3只雄性/3只雌性），其中庆大霉素被注射到水平半规管。
结果显示：1）前庭功能缺陷的量化可作为日常常规操作实现；2）水平半规管和耳石器官均可分别进行评估；3）UVL的损伤侧可被识别。
这些测试结果揭示了我们的系统作为评估小鼠常见前庭功能缺陷的标准设备的潜力。
