Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, USA.
Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts, USA.
J Clin Invest. 2024 Sep 24;134(22):e181201. doi: 10.1172/JCI181201.
The sensory cells that transduce the signals for hearing and balance are highly specialized mechanoreceptors called hair cells that together with supporting cells comprise the sensory epithelia of the inner ear. Loss of hair cells from toxin exposure and age can cause balance disorders and is essentially irreversible due to the inability of mammalian vestibular organs to regenerate physiologically active hair cells. Here, we show substantial regeneration of hair cells in a mouse model of vestibular damage by treatment with a combination of glycogen synthase kinase 3β and histone deacetylase inhibitors. The drugs stimulated supporting cell proliferation and differentiation into hair cells. The new hair cells were reinnervated by vestibular afferent neurons, rescuing otolith function by restoring head translation-evoked otolith afferent responses and vestibuloocular reflexes. Drugs that regenerate hair cells thus represent a potential therapeutic approach to the treatment of balance disorders.
将声音信号转化为听觉和平衡感觉的感觉细胞是高度特化的机械感受器，称为毛细胞。毛细胞与支持细胞一起构成内耳的感觉上皮。毛细胞因毒素暴露和年龄增长而丧失会导致平衡障碍，而且由于哺乳动物前庭器官无法生理性地再生有功能的毛细胞，这种丧失基本上是不可逆转的。在这里，我们通过使用糖原合酶激酶 3β和组蛋白去乙酰化酶抑制剂的组合治疗，在一种前庭损伤的小鼠模型中观察到毛细胞的大量再生。这些药物刺激了支持细胞的增殖和分化为毛细胞。新的毛细胞被前庭传入神经元重新支配，通过恢复头部平移诱发的耳石传入反应和前庭眼反射来恢复耳石功能。因此，能够再生毛细胞的药物代表了治疗平衡障碍的一种潜在治疗方法。
