Localization and pathogenesis of inner ear oxidative stress injury using NRF2 activation monitoring mice.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16825
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Tohoku University
• Principal Investigator: Oishi Tetsuya 東北大学, 医学系研究科, 非常勤講師 (30898995)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 内耳 / 酸化ストレス / NRF2 / シスプラチン難聴 / ラセン靭帯

Outline of Final Research Achievements

In order to detect the site of oxidative stress damage in the cochlea via activation of NRF2, we constructed and analyzed transgenic mice. The mice are capable of identifying the site of oxidative stress damage at the cellular level because red fluorescent expression is induced in the cells where oxidative stress occurs. When these mice were subjected to oxidative stress with cisplatin, many fluorescent-expressing cells were observed in the cochlea. Furthermore, observation of the distribution of fluorescent cells in the cochlea showed that they were mostly expressed in the lateral wall of the cochlea, such as the stria vascularis and spiral ligament, and at the spiral limbs, suggesting that these are the area vulnerable to oxidative stress injury.

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

NRF2の活性化は蝸牛における酸化ストレス障害を軽減させ、難聴の進行を抑制するという非常に重要な機能を持つと考えられる。
しかし、全身性のNRF2活性化マウスにおける加齢性難聴の解析では聴力低下の抑制が不十分な部分もあった。本研究では内耳の血管条やラセン靱帯といった蝸牛側壁や、ラセン板縁といった領域が酸化ストレス障害が生じやすいことが示唆され、その領域で特にNRF2活性化を誘導することが効果的な難聴治療・予防につながると考えられた。今後、これらの領域に着目し、更に検討を更に行うことで、酸化ストレス障害と関連した新たな分子機構の発見につながることも期待される。