Bovee Sonny, Jüchter Carolin, Klump Georg M, Köppl Christine, Pyott Sonja J
Department of Neuroscience, School of Medicine and Health Science, Carl von Ossietzky Universität Oldenburg, Oldenburg 26129, Germany; The Research School of Behavioural and Cognitive Neurosciences, University of Groningen, PO Box 30.001, Groningen 9700 RB, the Netherlands.
Department of Neuroscience, School of Medicine and Health Science, Carl von Ossietzky Universität Oldenburg, Oldenburg 26129, Germany.
Neurobiol Aging. 2025 Aug 14;156:50-62. doi: 10.1016/j.neurobiolaging.2025.08.004.
Presbycusis, or age-related hearing loss, is a prevalent condition characterized by progressive auditory decline, significantly impacting quality of life in older adults. While sensorineural damage has been widely studied, degeneration of the stria vascularis (SV) remains underexplored despite its essential role in cochlear ion homeostasis. The SV is organized into three cellular layers-marginal, intermediate, and basal cells-each with distinct functions critical for maintaining the endocochlear potential. Using the quiet-aged Mongolian gerbil-a well-established model of metabolic presbycusis-we systematically mapped the structural and cellular degeneration of the SV and linked these changes to cochlear function. We assessed cochlear function using auditory brainstem response (ABR) measurements and quantified age-related atrophy of the strial cell layers using immunofluorescence, confocal microscopy, and 3D reconstruction. We identified a striking, region-specific pattern of degeneration, with the greatest atrophy occurring in ATP1A1-expressing marginal cells, followed by KCNJ10-expressing intermediate cells, and comparatively little atrophy in CLDN11-expressing basal cells. Notably, atrophy was most pronounced in the cochlear apex and base, regions critical for low- and high-frequency hearing. We further established a significant correlation between the decline in cochlear function and the extent of atrophy of the individual strial cell layers, especially in the cochlear base. By moving beyond traditional cross-sectional assessments of age-related degeneration of the SV, this work provides a more nuanced understanding of how strial pathology contributes to age-related decline in cochlear function and may inform therapeutic interventions targeting strial function to mitigate age-related hearing loss even when sensorineural function is compromised.
老年性聋，即与年龄相关的听力损失，是一种普遍存在的病症，其特征为进行性听力衰退，对老年人的生活质量有显著影响。虽然感觉神经性损伤已得到广泛研究，但血管纹（SV）的退化尽管在耳蜗离子稳态中起关键作用，却仍未得到充分探索。血管纹由三层细胞组成——边缘细胞、中间细胞和基底细胞——每层细胞都具有维持内淋巴电位所必需的独特功能。我们使用安静老年蒙古沙鼠（一种成熟的代谢性老年性聋模型），系统地绘制了血管纹的结构和细胞退化情况，并将这些变化与耳蜗功能联系起来。我们通过听觉脑干反应（ABR）测量评估耳蜗功能，并使用免疫荧光、共聚焦显微镜和三维重建技术量化血管纹细胞层与年龄相关的萎缩情况。我们发现了一种显著的、区域特异性的退化模式，其中表达ATP1A1的边缘细胞萎缩最为严重，其次是表达KCNJ10的中间细胞，而表达CLDN11的基底细胞萎缩相对较少。值得注意的是，萎缩在耳蜗顶端和基部最为明显，这两个区域对低频和高频听力至关重要。我们进一步确定了耳蜗功能下降与各个血管纹细胞层萎缩程度之间存在显著相关性，尤其是在耳蜗基部。通过超越传统的血管纹与年龄相关退化的横断面评估，这项研究对血管纹病理学如何导致耳蜗功能与年龄相关的下降提供了更细致入微的理解，并可能为针对血管纹功能的治疗干预提供依据，以减轻与年龄相关的听力损失，即使在感觉神经功能受损时也是如此。
