ArticleProceedings of the National Academy of Sciences of the United States of America2022
In vivo real-time imaging reveals megalin as the aminoglycoside gentamicin transporter into cochlea whose inhibition is otoprotective.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 39 citations in OpenAlex.
- Pharmacotherapeutic Interventions for Sensorineural Hearing Loss: A Scoping Review.Audiology research · 2026Review
- Spontaneous Calcium Signalling in the Developing Mammalian Cochlea.Journal of the Association for Research in Otolaryngology : JARO · 2026Review
- Discovery of a Novel Non-MET-Mediated Otoprotective Compound Against Aminoglycoside-Induced Ototoxicity.bioRxiv : the preprint server for biology · 2026Article
- TRPV4 mediates aminoglycoside trafficking and ototoxicity without compromising antimicrobial efficacy.Cell death discovery · 2026Article
- Navigating the Genetic Risk of Chemotherapy-Induced Hearing Loss in the Stria Vascularis.Clinical pharmacology and therapeutics · 2026Review
- Spontaneous CaExperimental physiology · 2026Article
- Engineered Inner Ear Drug Delivery Systems for Hearing Loss Treatment.Research (Washington, D.C.) · 2026Review
- The aryl hydrocarbon receptor is expressed in non-sensory cells in the cochlea and regulates hair cell survival.Frontiers in molecular neuroscience · 2026Article
- Infrared light stimulates the cochlea through a mechanical displacement detected and amplified by hair cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanisms driving the functional maturation of the developing mammalian auditory pathway.Current topics in developmental biology · 2025Review
- Semicircular canal drug delivery safely targets the inner ear perilymphatic space.JCI insight · 2024Article
- Endolymphatic hydrops and cochlear synaptopathy after noise exposure are distinct sequelae of hair cell stereociliary bundle trauma.Scientific reports · 2024Article
- Pharmacological Approaches to Hearing Loss.Pharmacological reviews · 2024Review
- Piplartine attenuates aminoglycoside-induced TRPV1 activity and protects from hearing loss in mice.Science translational medicine · 2024Article
- Cryo-EM structures elucidate the multiligand receptor nature of megalin.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The multifaceted links between hearing loss and chronic kidney disease.Nature reviews. Nephrology · 2024Review
- Large-scale annotated dataset for cochlear hair cell detection and classification.Scientific data · 2024Article
- Age-related alterations in efferent medial olivocochlear-outer hair cell and primary auditory ribbon synapses in CBA/J mice.Frontiers in cellular neuroscience · 2024Article
- Otoprotection against aminoglycoside- and cisplatin-induced ototoxicity focusing on the upstream drug uptake pathway.Journal of the Chinese Medical Association : JCMA · 2024Review
- The Cousa objective: a long-working distance air objective for multiphoton imaging in vivo.Nature methods · 2024Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Aminoglycosides (AGs) are commonly used antibiotics that cause deafness through the irreversible loss of cochlear sensory hair cells (HCs). How AGs enter the cochlea and then target HCs remains unresolved. Here, we performed time-lapse multicellular imaging of cochlea in live adult hearing mice via a chemo-mechanical cochleostomy. The in vivo tracking revealed that systemically administered Texas Red-labeled gentamicin (GTTR) enters the cochlea via the stria vascularis and then HCs selectively. GTTR uptake into HCs was completely abolished in transmembrane channel-like protein 1 (TMC1) knockout mice, indicating mechanotransducer channel-dependent AG uptake. Blockage of megalin, the candidate AG transporter in the stria vascularis, by binding competitor cilastatin prevented GTTR accumulation in HCs. Furthermore, cilastatin treatment markedly reduced AG-induced HC degeneration and hearing loss in vivo. Together, our in vivo real-time tracking of megalin-dependent AG transport across the blood-labyrinth barrier identifies new therapeutic targets for preventing AG-induced ototoxicity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.