ZeTox – Toxicology Services

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icon-oto-tox OtoTox – Ototoxicology Services

Hair cells are mechanosensory receptors of the inner ear and can be damaged by noise, aging, and ototoxic drugs like aminoglycosides and platinum derivatives. Fish and mammalian hair cells are sensitive to the same chemical and acoustic inputs.

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.

Advantages

Zebrafish lateral line hair cells are identical to mammalian inner ear hair cells.

Presence of hair cells on zebrafish larvae body surface, which facilitates drug administration and cell visualization.

Evaluation of potential otoprotective candidates.

Method description

Transgenic zebrafish larvae expressing green fluorescent protein in hair cells are exposed to the compound of interest. Neuromasts hair cells from the posterior lateral line are imaged and counted. Optionally, larvae can be incubated with another live dye to visualize functional hair cells.

Readouts

Visual analysis of hair cells at 120 hpf:

  • Total hair cell number
  • Functional hair cells (optional)
Figure 2. Quantification of hair cell cytotoxicity. (A) Neuromast hair cell counting of larvae treated with different concentrations of two ototoxic compounds compared to negative control. (B) Images of neuromast hair cells expressing green fluorescent protein after the exposure to the above concentrations of toxic compounds and negative control.

References

  1. Monroe JD, Rajadinakaran G, Smith ME. Sensory hair cell death and regeneration in fishes. Front Cell Neurosci. 2015 Apr 21;9:131.
  2. Ton C, Parng C. The use of zebrafish for assessing ototoxic and otoprotective agents. Hear Res. 2005 Oct;208(1-2):79-88.
  3. Chiu LL, Cunningham LL, Raible DW, Rubel EW, Ou HC. Using the zebrafish lateral line to screen for ototoxicity. J Assoc Res Otolaryngol. 2008 Jun;9(2):178-90.