AUTHOR=Bellairs Joseph A. , Redila Van A. , Wu Patricia , Tong Ling , Webster Alyssa , Simon Julian A. , Rubel Edwin W. , Raible David W. TITLE=An in vivo Biomarker to Characterize Ototoxic Compounds and Novel Protective Therapeutics JOURNAL=Frontiers in Molecular Neuroscience VOLUME=15 YEAR=2022 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.944846 DOI=10.3389/fnmol.2022.944846 ISSN=1662-5099 ABSTRACT=
There are no approved therapeutics for the prevention of hearing loss and vestibular dysfunction from drugs like aminoglycoside antibiotics. While the mechanisms underlying aminoglycoside ototoxicity remain unresolved, there is considerable evidence that aminoglycosides enter inner ear mechanosensory hair cells through the mechanoelectrical transduction (MET) channel. Inhibition of MET-dependent uptake with small molecules or modified aminoglycosides is a promising otoprotective strategy. To better characterize mammalian ototoxicity and aid in the translation of emerging therapeutics, a biomarker is needed. In the present study we propose that neonatal mice systemically injected with the aminoglycosides G418 conjugated to Texas Red (G418-TR) can be used as a histologic biomarker to characterize