Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA 02114, USA; Dept of Otolaryngology-Head & Neck Surgery, Harvard Medical School, Boston, MA 02115, USA.
Northeastern University, Boston, MA 02115, USA.
Hear Res. 2023 Aug;435:108815. doi: 10.1016/j.heares.2023.108815. Epub 2023 May 25.
Animal studies have shown that the supporting-cells surviving in the organ of Corti after cochlear insult can be transdifferentiated into hair cells as a treatment for sensorineural hearing loss. Clinical trials of small-molecule therapeutics have been undertaken, but little is known about how to predict the pattern and degree of supporting-cell survival based on audiogram, hearing loss etiology or any other metric obtainable pre-mortem. To address this, we systematically assessed supporting-cell and hair cell survival, as a function of cochlear location in 274 temporal bone cases from the archives at the Massachusetts Eye and Ear and compared the histopathology with the audiograms and hearing-loss etiologies. Results showed that supporting-cell survival was always significantly greater in the apical half than the basal half of the cochlea, that inner pillars were more robust than outer pillars or Deiters' cells, and that total replacement of all supporting cells with a flat epithelium was rare outside of the extreme basal 20% of the cochlea. Supporting cell survival in the basal half of the cochlea was better correlated with the slope of the audiogram than with the mean high-frequency threshold per se: i.e. survival was better with flatter audiograms than with steeply down-sloping audiograms. Cochlear regions with extensive hair cell loss and exceptional supporting cell survival were most common in cases with hearing loss due to ototoxic drugs. Such cases also tended to have less pathology in other functionally critical structures, i.e. spiral ganglion neurons and the stria vascularis.
动物研究表明，耳蜗损伤后幸存的支持细胞可以转分化为毛细胞，作为治疗感音神经性听力损失的一种方法。已经进行了小分子治疗的临床试验，但对于如何根据听力图、听力损失病因或任何其他可在生前获得的指标来预测支持细胞存活的模式和程度，知之甚少。为了解决这个问题，我们系统地评估了 274 例来自马萨诸塞州眼耳档案馆颞骨标本的支持细胞和毛细胞的存活情况，这些标本的位置与耳蜗有关，并将组织病理学与听力图和听力损失病因进行了比较。结果表明，支持细胞的存活在耳蜗的顶部总是明显高于底部，内柱比外柱或 Deiters 细胞更坚固，除了耳蜗最极端的底部 20%之外，很少有全部支持细胞被扁平上皮替代。耳蜗底部的支持细胞存活与听力图的斜率比与平均高频阈值本身的相关性更好：即听力图越平坦，存活情况越好，而听力图急剧下降的情况则较差。耳蜗区域的毛细胞大量丢失和支持细胞异常存活最常见于因耳毒性药物引起的听力损失病例。这些病例在其他功能关键结构（即螺旋神经节神经元和血管纹）中的病变也较少。
