UCL Ear Institute, University College London, London, UK.
Sussex Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton, UK.
J Neurosci Res. 2020 Sep;98(9):1745-1763. doi: 10.1002/jnr.24556. Epub 2019 Nov 24.
The aging cochlea is subjected to a number of pathological changes to play a role in the onset of age-related hearing loss (ARHL). Although ARHL has often been thought of as the result of the loss of hair cells, it is in fact a disorder with a complex etiology, arising from the changes to both the organ of Corti and its supporting structures. In this study, we examine two aging pathologies that have not been studied in detail despite their apparent prevalence; the fusion, elongation, and engulfment of cochlear inner hair cell stereocilia, and the changes that occur to the tectorial membrane (TM), a structure overlying the organ of Corti that modulates its physical properties in response to sound. Our work demonstrates that similar pathological changes occur in these two structures in the aging cochleae of both mice and humans, examines the ultrastructural changes that underlie stereocilial fusion, and identifies the lost TM components that lead to changes in membrane structure. We place these changes into the context of the wider pathology of the aging cochlea, and identify how they may be important in particular for understanding the more subtle hearing pathologies that precede auditory threshold loss in ARHL.
衰老的耳蜗会经历多种病理变化,从而导致与年龄相关的听力损失(ARHL)。尽管 ARHL 通常被认为是毛细胞丧失的结果,但实际上它是一种病因复杂的疾病,源于 Corti 器官及其支持结构的变化。在这项研究中,我们研究了两种尽管明显普遍存在但尚未详细研究的衰老病理学;耳蜗内毛细胞静纤毛的融合、延长和吞噬,以及覆盖 Corti 器官的听小膜(TM)发生的变化,该结构调节其物理特性以响应声音。我们的工作表明,在小鼠和人类衰老耳蜗的这两种结构中都存在类似的病理变化,检查了静纤毛融合的基础超微结构变化,并确定了导致膜结构变化的丢失 TM 成分。我们将这些变化置于衰老耳蜗更广泛病理学的背景下,并确定它们如何对理解 ARHL 中听觉阈值丧失之前出现的更微妙听力病理学特别重要。