Systemic Fluorescent Gentamicin Enters Neonatal Mouse Hair Cells Predominantly Through Mechanoelectrical Transduction Channels

2017 Fiscal Year Final Research Report

• Project/Area Number: 26462551
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KAWASHIMA Yoshiyuki 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (10376759)
• Co-Investigator(Kenkyū-buntansha): 野口 佳裕 信州大学, 医学部, 特任教授 (50282752)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 内耳 / 有毛細胞 / アミノグリコシド系抗菌薬 / TMC1 / TMC2

Outline of Final Research Achievements

Systemically administered aminoglycoside antibiotics enter the inner ear hair cells and trigger apoptosis. However, the in vivo mechanisms by which aminoglycoside antibiotics enter hair cells remain controversial. Transmembrane channel-like 1 (TMC1) and TMC2 are essential for MET and are components of the stereocilia MET channel complex. The present study aimed to clarify that systemic fluorescent gentamicin enters mouse hair cells through MET channels. Gentamicin-conjugated Texas Red (GTTR) or PBS was subcutaneously injected into Tmc1Δ;Tmc2Δ mice and wild-type mice at postnatal day 0 (P0), P2, P4, or P6. In Tmc1Δ;Tmc2Δ mice, the intensity was mostly stable from P0 through P6. In wild-type mice, the GTTR fluorescent intensity gradually increased with the development of hair cells. The increase in the GTTR intensity in wild-type mice coincided with the spatiotemporal onset of MET. These results provide evidence that AGs enter hair cells predominantly through MET channels.

Free Research Field

耳科学