Open AccessIn vivo real-time imaging reveals megalin as the aminoglycoside gentamicin transporter into cochlea whose inhibition is otoprotective
Author(s) -
JinKyung Kim,
Anthony J. Ricci
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2117946119
Subject(s) - cochlea , in vivo , aminoglycoside , ototoxicity , chemistry , microbiology and biotechnology , inner ear , hearing loss , pharmacology , medicine , biology , anatomy , antibiotics , biochemistry , audiology , chemotherapy , cisplatin
Significance Ototoxicity is a major side effect of aminoglycoside (AG) antibiotics; however, the mechanism by which this drug enters the cochlea and target hair cells (HCs) is not fully understood. Here, we developed an in vivo cochlear imaging method that enables real-time tracking of ototoxic drug transport into the cochlea in hearing adult mice. The time-lapse monitoring of drugs identified megalin as the major transporter of AG into the endolymph and the mechanotransducer channels as the portal into the HCs. Blocking megalin in vivo prevents AG-induced ototoxicity. Therefore, this study identifies an AG uptake pathway into the cochlea and provides a therapeutic target to eliminate drug-induced hearing loss.