Zhu Bovey Z, Saleh Jasmine, Isgrig Kevin T, Cunningham Lisa L, Chien Wade W
Neurotology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
Audiol Neurootol. 2016;21(6):356-364. doi: 10.1159/000449239. Epub 2017 Jan 10.
Delivery of therapeutic agents directly through the round window (RW) offers promise for treating sensorineural hearing loss. However, hearing loss can result from the surgical approach itself, and the reasons for this are poorly understood. We examined the hearing loss following the 3 major steps involved with the RW approach to access the mouse cochlea: bullostomy, RW puncture, and RW injection.
Twenty-one adult CBA/J mice underwent bullostomy alone, 10 underwent RW puncture, and 8 underwent RW injection with PBS with 5% glycerol. Auditory brainstem responses (ABR) and otoscopy were performed preoperatively and up to 6 weeks postoperatively. Hair cells were stained, and survival was assessed using immunofluorescence.
One week postoperatively, mice in all groups showed significant threshold shifts. Otoscopy revealed approximately half of all mice had middle ear effusion (MEE), with a higher incidence of effusion in the RW puncture and RW injection groups. Those with MEE had significant ABR threshold shifts, whereas those without MEE had minimal hearing loss. MEE persisted through 6 weeks in a majority of cases, but in those mice with MEE resolution, there was at least partial improvement in hearing. Immunohistochemistry showed minimal loss of hair cells in all animals.
MEE is highly correlated with hearing loss in mice undergoing RW surgery. Otoscopy is an important adjunct to consider after ear surgery in mice, as MEE may contribute to postsurgical hearing loss.
通过圆窗直接递送治疗剂为治疗感音神经性听力损失带来了希望。然而,听力损失可能由手术方法本身导致,而其原因尚不清楚。我们研究了采用圆窗入路进入小鼠耳蜗所涉及的三个主要步骤(鼓泡造口术、圆窗穿刺和圆窗注射)后的听力损失情况。
21只成年CBA/J小鼠仅接受鼓泡造口术,10只接受圆窗穿刺,8只接受用含5%甘油的磷酸盐缓冲盐水进行圆窗注射。术前及术后长达6周进行听觉脑干反应(ABR)测试和耳镜检查。对毛细胞进行染色,并使用免疫荧光评估其存活情况。
术后1周,所有组的小鼠均出现明显的阈值变化。耳镜检查显示,约一半的小鼠有中耳积液(MEE),圆窗穿刺组和圆窗注射组的积液发生率更高。有MEE的小鼠ABR阈值有明显变化,而没有MEE的小鼠听力损失最小。在大多数情况下,MEE持续6周,但在MEE消退的小鼠中,听力至少有部分改善。免疫组织化学显示所有动物的毛细胞损失极少。
MEE与接受圆窗手术的小鼠的听力损失高度相关。耳镜检查是小鼠耳部手术后需要考虑的一项重要辅助检查,因为MEE可能导致术后听力损失。