Regeneration of primary auditory neurons by in vivo reprogramming

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18767
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Teikyo University (2020-2021); Kyoto University (2019)
• Principal Investigator: Nishimura Koji 帝京大学, 医学部, 講師 (20405765)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: リプログラミング / 蝸牛神経 / 転写因子

Outline of Final Research Achievements

Our aim was to regenerate primary auditory neurons in vivo by direct reprogramming and to develop a novel method for curing patients with profound sensorineural hearing loss whose primary auditory neurons are severely affected. We injected cardiac glycosides such as ouabain and digoxin into the inner ear of mice and guinea pigs, and we performed histological and electrophysiological assessment of degeneration of primary auditory neurons as well as primary vestibular neurons. Neurogenic genes of interest were not efficiently introduced into Schwann cells in the spiral ganglia by AAV2 or Anc80 serotypes, and we need to test other serotypes of AAV and promoters that drive the expression of neurogenic transcription factors.

Free Research Field

聴覚医学、分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

人工内耳手術を受ける高度感音難聴者の蝸牛神経が健聴者と同程度に再生され、蝸牛有毛細胞の機能により近似した人工内耳が開発されれば、人工内耳装用者も健聴者と同程度の聴覚の質が担保されると考えられる。in vivoでのラセン神経節の障害モデルの作製および遺伝子導入法の確立は一度変性したラセン神経を再生させる方法の開発に必要である。同時に、前庭神経節内の易障害性神経節細胞やシュワン細胞の解析は加齢性および薬剤性の平衡障害メカニズムの解明や治療に寄与すると考えられる。