Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Neurosci Lett. 2021 Mar 16;747:135679. doi: 10.1016/j.neulet.2021.135679. Epub 2021 Jan 29.
Vestibular hair cells (HCs) are mechanoreceptors for the detection of head movement. Vestibular HCs of adult mammals never completely regenerate after damage, resulting in vestibular dysfunction. Overexpression of Atoh1 is effective for inducing HC regeneration. However, method of clinical feasibility and improvement of regenerative extent are both in need. Here we used an adeno-associated virus (AAV) serotype 8 vector of two different titers to overexpress Atoh1 in the injured utricles of adult mice. One month after virus inoculation, abundant myosin VIIa-positive cells and immature stereocilia were observed. Quantitative analyses revealed that Atoh1 overexpression replenished vestibular HCs in a dose-dependent manner. Vectors of a higher titer increased the number of myosin VIIa-positive cells compared to those of lower titer. Moreover, only Atoh1 overexpression in the higher titer group enhanced stereocilium regeneration, which is an important step in the maturation of regenerated HCs. Although the current treatment failed to initiate functional recovery of the animals, our results prompt further improvements in the recovery of vestibular dysfunction by AAV.
前庭毛细胞 (HCs) 是检测头部运动的机械感受器。成年哺乳动物的前庭 HCs 在损伤后从未完全再生，导致前庭功能障碍。Atoh1 的过表达可有效诱导 HC 再生。然而，临床可行性的方法和再生程度的提高都需要进一步研究。在这里，我们使用两种不同滴度的腺相关病毒 (AAV) 血清型 8 载体在成年小鼠受损的前庭中过表达 Atoh1。病毒接种一个月后，观察到大量肌球蛋白 VIIa 阳性细胞和未成熟的静纤毛。定量分析表明，Atoh1 的过表达以剂量依赖性方式补充前庭 HCs。与低滴度载体相比，高滴度载体增加了肌球蛋白 VIIa 阳性细胞的数量。此外，只有高滴度组的 Atoh1 过表达增强了静纤毛的再生，这是再生 HCs 成熟的重要步骤。尽管目前的治疗未能使动物的功能恢复，但我们的结果促使进一步改进 AAV 治疗前庭功能障碍的恢复。
