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Hearing Loss Model

Several factors can lead to hearing loss in humans, including aging (degeneration of inner ear structures occurs over time), repetitive exposure to moderate or loud noise and genetic heredity. Loss of hearing sensitivity is due to damage or loss of Hair Cells (HC) and nerve cells in the inner ear.

Zebrafish display an external sensory system, called lateral line, required for the detection of local water displacements and vibration. The lateral line, absent in mammals, comprises a number of individual sense organs, the neuromasts, composed by HC rosettes and arranged in a defined pattern in the surface of the body. HC neuromast and human inner ear HCs show a high degree of morphological, physiological and genetic conservation. 

These features make zebrafish a well-established model in hearing research, providing a unique opportunity to investigate the molecular and physiological mechanisms of hearing loss at the sensory receptor level. We offer a ready-to-use pharmacological model for the study of the inner ear and hearing system as well as for screening new oto-protective or oto-regenerative therapeutic drugs.

Figure 1. Morphology of the lateral line of zebrafish. Lateral and dorsal views of zebrafish larvae showing the stereotyped distribution of neuromasts along the body. The zoom in shows a schematic representation of a single neuromast and its major anatomical features.

Applications

  • Study hearing regeneration.
  • Study the molecular and physiological mechanisms of hearing loss.
  • High throughput screening of new therapeutic compounds for this condition.

Advantages

Zebrafish share homologous inner ear structures to mammals and have the ability to regenerate HC.

Accessibility to the hair cells on the lateral line.

Fast development of the lateral line sensory system.

Transparency of the model.

Method description

Neomycin, an antibiotic inducing HC death, is administered to transgenic tg(brn3c:mGFP) zebrafish larvae expressing green fluorescent protein (GFP) in hair cells. After damage, larvae are exposed to previously determined concentrations of the compound of interest.

Larvae are then incubated with a live dye staining functional HCs specifically. Finally, HCs of the first two posterior lateral line neuromasts on both sides are counted at different time points, with the help of image analysis custom software.

Figure 1. Posterior macula reconstruction.

Readouts

  • Hair cells: total and fully functional neuromasts HC counting through microscope at three time points.