Zebrafish models of sensorineural hearing loss

Abstract

Sensorineural hearing loss negatively impacts over 450 million people worldwide. While we know that insults such as ototoxic drugs and noise damage sensory hair cells, our understanding of damage mechanisms is incomplete. Zebrafish are an exciting vertebrate model for research on fundamental mechanisms of hair cell damage. In addition to the inner ear, zebrafish have a lateral line system containing clusters of externally located hair cells. These hair cells are homologous to vertebrate inner ear hair cells and respond similarly to ototoxic damage. Our lab uses the lateral line system to determine the ototoxic potential of COVID-19 therapies; with over 900 medications currently in clinical trials, it is highly likely that a subset of those medications causes mild hearing loss that is not detected in clinical settings. In addition, while ototoxicity is a significant concern for patients exposed to these medications, acoustic damage and age-related hearing loss are far more prevalent in the general population. Our lab developed a zebrafish model of acoustic trauma and showed that noise exposure causes synaptic damage and hair cell loss in the larval lateral line analogous to the damage observed in the mammalian cochlea. Finally, we show that aged adult zebrafish lose both lateral line and inner ear hair cells similar to hair cell loss seen in aging mammals. Collectively, our research demonstrates that zebrafish are a tractable model to understand mechanisms of sensorineural hearing loss and to test therapeutic strategies.