Usage Information
Citation Information: JCI Insight. 2021;6(7):e145704. https://doi.org/10.1172/jci.insight.145704.
Abstract
To identify small molecules that shield mammalian sensory hair cells from the ototoxic side effects of aminoglycoside antibiotics, 10,240 compounds were initially screened in zebrafish larvae, selecting for those that protected lateral-line hair cells against neomycin and gentamicin. When the 64 hits from this screen were retested in mouse cochlear cultures, 8 protected outer hair cells (OHCs) from gentamicin in vitro without causing hair-bundle damage. These 8 hits shared structural features and blocked, to varying degrees, the OHC’s mechano-electrical transducer (MET) channel, a route of aminoglycoside entry into hair cells. Further characterization of one of the strongest MET channel blockers, UoS-7692, revealed it additionally protected against kanamycin and tobramycin and did not abrogate the bactericidal activity of gentamicin. UoS-7692 behaved, like the aminoglycosides, as a permeant blocker of the MET channel; significantly reduced gentamicin–Texas red loading into OHCs; and preserved lateral-line function in neomycin-treated zebrafish. Transtympanic injection of UoS-7692 protected mouse OHCs from furosemide/kanamycin exposure in vivo and partially preserved hearing. The results confirmed the hair-cell MET channel as a viable target for the identification of compounds that protect the cochlea from aminoglycosides and provide a series of hit compounds that will inform the design of future otoprotectants.
Authors
Emma J. Kenyon, Nerissa K. Kirkwood, Siân R. Kitcher, Richard J. Goodyear, Marco Derudas, Daire M. Cantillon, Sarah Baxendale, Antonio de la Vega de León, Virginia N. Mahieu, Richard T. Osgood, Charlotte Donald Wilson, James C. Bull, Simon J. Waddell, Tanya T. Whitfield, Simon E. Ward, Corné J. Kros, Guy P. Richardson
Usage data is cumulative from September 2023 through September 2024.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 682 | 406 |
| 80 | 81 | |
| Figure | 261 | 21 |
| Supplemental data | 63 | 15 |
| Citation downloads | 32 | 0 |
| Totals | 1,118 | 523 |
| Total Views | 1,641 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
