Larval Zebrafish Lateral Line as a Model for Acoustic Trauma

Abstract

Excessive noise exposure damages sensory hair cells, leading to permanent hearing loss. Zebrafish are a highly tractable model that have advanced our understanding of drug-induced hair cell death, yet no comparable model exists for noise exposure research. We demonstrate the utility of zebrafish as model to increase understanding of hair cell damage from acoustic trauma and develop protective therapies. We created an acoustic trauma system using underwater cavitation to stimulate lateral line hair cells. We found that acoustic stimulation resulted in exposure time- and intensity-dependent lateral line and saccular hair cell damage that is maximal at 48-72h post-trauma. The number of TUNEL positive lateral line hair cells increased 72h post-exposure whereas no increase was observed in TUNEL positive supporting cells, demonstrating that acoustic stimulation causes hair cell-specific damage. Lateral line hair cells damaged by acoustic stimulation regenerate within three days, consistent with prior regeneration studies utilizing ototoxic drugs. Acoustic stimulation-induced hair cell damage is attenuated by pharmacological inhibition of protein synthesis or caspase activation, suggesting a requirement for translation and activation of apoptotic signaling cascades. Surviving hair cells exposed to acoustic stimulation showed signs of synaptopathy, consistent with mammalian studies. Finally, we demonstrate the feasibility of this platform to identify compounds that prevent acoustic trauma by screening a small redox library for protective compounds. Our data suggest that acoustic stimulation results in lateral line hair cell damage consistent with acoustic trauma research in mammals, providing a highly tractable model for high-throughput genetic and drug discovery studies.

Significance Statement Noise overexposure damages hair cells, leading to permanent hearing loss. A critical step in understanding and preventing noise-induced hearing loss is establishing an accessible in vivo model to test for genetic and chemical modulators of noise damage. We developed a novel acoustic trauma system, using cavitation, to stimulate and damage zebrafish lateral line hair cells. We demonstrate that acoustic stimulation damages zebrafish lateral line hair cells in an exposure time- and intensity-dependent manner, consistent with acoustic trauma research in mammals. This novel system provides a model for in vivo, real-time studies of noise exposure, and for rapid discovery of chemical and genetic modulators of acoustic trauma-induced hair cell damage.