In vivo real-time imaging reveals megalin as the aminoglycoside gentamicin transporter into cochlea whose inhibition is otoprotective

TLDR: An in vivo cochlear imaging method is developed that enables real-time tracking of ototoxic drug transport into the cochlea in hearing adult mice and provides a therapeutic target to eliminate drug-induced hearing loss.

Abstract: 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.