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In vivo real-time imaging reveals megalin as the aminoglycoside gentamicin transporter into cochlea whose inhibition is otoprotective Jinkyung Kim and Anthony J. Ricci Aminoglycoside antibiotics are commonly used to treat bacterial infections; more than 10 million doses of this class of antibiotics are used each year in the United States alone to treat Gram-negative bacterial infections and sepsis. However, these antibiotics can cause hearing loss by damaging cochlear sensory hair cells. How aminoglycosides enter the cochlea and target hair cells is unclear. The authors of this study performed real-time tracking of gentamicin, an aminoglycoside, from the bloodstream into the cochlea of adult mice with normal hearing. A surgical approach enabled time-lapse imaging of gentamicin being delivered into a specialized compartment—the endolymph—of the cochlea by the transporter protein megalin and, subsequently, into hair cells. Cilastatin, a competitive blocker of megalin, reduced gentamicin accumulation in hair cells and gentamicin-induced hearing loss. The study identifies a therapeutic target for preventing antibiotic-induced hearing loss. Read the award-winning research article: https://www.pnas.org/doi/10.1073/pnas... For more information about the Proceedings of the National Academy of Sciences, visit www.pnas.org.