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<p>Vesicular glutamate transporter 3 (VGLUT3) is prominently expressed in the inner hair cells of the cochlea, playing a vital role in auditory signal transmission to the brain. Previous studies have shown that <i>Vglut3</i> gene knockout in mice causes severe sensorineural hearing loss without affecting hair cell integrity. However, the cochlear structure of the aged <i>Vglut3</i><sup><i>KO</i></sup> remains inadequately explored. In this study, we analyzed the cochlear structure of aged <i>Vglut3</i><sup><i>KO</i></sup> mice, revealing significant degeneration of inner hair cells, synapses, and stereocilia. To explore the potential of gene therapy to restore cochlear structure, we employed AAV8 vectors to express <i>Vglut3</i> in the cochleae of 5-week-old <i>Vglut3</i><sup><i>KO</i></sup> mice. Twenty-seven weeks post-injection, we conducted a series of experiments to evaluate the efficacy of our gene therapy approach. Auditory brainstem response (ABR) testing demonstrated restoration of auditory function following gene therapy. Immunohistochemical staining and scanning electron microscopy (SEM) analysis revealed substantial recovery of inner hair cells and stereocilia post-injection. Our findings provide important insights into the development of novel therapeutic strategies for age-related hearing loss.</p>

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Gene therapy restores auditory function and rescues damaged inner hair cells in an aged Vglut3 knockout mouse model

  • 期刊论文

  • 发表日期：

    2025年8月21日

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  • Xingle Zhao,
  • Hongen Xu,
  • Chengyu Lian,
  • Shousen Hu,
  • Yue Zhao,
  • Jia Wang,
  • Rongqun Zhai,
  • Mihuan Yang,
  • Yuanjing Zhang,
  • Wei Lu,
  • Wenxue Tang,
  • Liang Wang

摘要

Vesicular glutamate transporter 3 (VGLUT3) is prominently expressed in the inner hair cells of the cochlea, playing a vital role in auditory signal transmission to the brain. Previous studies have shown that Vglut3 gene knockout in mice causes severe sensorineural hearing loss without affecting hair cell integrity. However, the cochlear structure of the aged Vglut3KO remains inadequately explored. In this study, we analyzed the cochlear structure of aged Vglut3KO mice, revealing significant degeneration of inner hair cells, synapses, and stereocilia. To explore the potential of gene therapy to restore cochlear structure, we employed AAV8 vectors to express Vglut3 in the cochleae of 5-week-old Vglut3KO mice. Twenty-seven weeks post-injection, we conducted a series of experiments to evaluate the efficacy of our gene therapy approach. Auditory brainstem response (ABR) testing demonstrated restoration of auditory function following gene therapy. Immunohistochemical staining and scanning electron microscopy (SEM) analysis revealed substantial recovery of inner hair cells and stereocilia post-injection. Our findings provide important insights into the development of novel therapeutic strategies for age-related hearing loss.