Wang Guo-Peng, Basu Ishani, Beyer Lisa A, Wong Hiu Tung, Swiderski Donald L, Gong Shu-Sheng, Raphael Yehoash
Department of Otolaryngology - Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China; Kresge Hearing Research Institute, Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Kresge Hearing Research Institute, Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Hear Res. 2017 Nov;355:33-41. doi: 10.1016/j.heares.2017.09.004. Epub 2017 Sep 11.
The damaged vestibular sensory epithelium of mammals has a limited capacity for spontaneous hair cell regeneration, which largely depends on the transdifferentiation of surviving supporting cells. Little is known about the response of vestibular supporting cells to a severe insult. In the present study, we evaluated the impact of a severe ototoxic insult on the histology of utricular supporting cells and the changes in innervation that ensued. We infused a high dose of streptomycin into the mouse posterior semicircular canal to induce a severe lesion in the utricle. Both scanning electron microscopy and light microscopy of plastic sections showed replacement of the normal cytoarchitecture of the epithelial layer with a flat layer of cells in most of the samples. Immunofluorescence staining showed numerous cells in the severely damaged epithelial layer that were negative for hair cell and supporting cell markers. Nerve fibers under the flat epithelium had high density at the 1 month time point but very low density by 3 months. Similarly, the number of vestibular ganglion neurons was unchanged at 1 month after the lesion, but was significantly lower at 3 months. We therefore determined that the mouse utricular epithelium turns into a flat epithelium after a severe lesion, but the degeneration of neural components is slow, suggesting that treatments to restore balance by hair cell regeneration, stem cell therapy or vestibular prosthesis implantation will likely benefit from the short term preservation of the neural substrate.
哺乳动物受损的前庭感觉上皮自发毛细胞再生能力有限，这在很大程度上依赖于存活支持细胞的转分化。关于前庭支持细胞对严重损伤的反应，人们了解甚少。在本研究中，我们评估了严重耳毒性损伤对椭圆囊支持细胞组织学的影响以及随之而来的神经支配变化。我们将高剂量链霉素注入小鼠后半规管以诱导椭圆囊严重损伤。扫描电子显微镜和塑料切片的光学显微镜检查均显示，大多数样本中上皮层的正常细胞结构被一层扁平细胞所取代。免疫荧光染色显示，严重受损的上皮层中有许多细胞对毛细胞和支持细胞标志物呈阴性。扁平上皮下方的神经纤维在1个月时密度较高，但到3个月时密度极低。同样，损伤后1个月时前庭神经节神经元数量未变，但3个月时显著减少。因此，我们确定小鼠椭圆囊上皮在严重损伤后会变成扁平上皮，但神经成分的退化较为缓慢，这表明通过毛细胞再生、干细胞治疗或前庭假体植入来恢复平衡的治疗方法可能会受益于神经基质的短期保存。
