Abstract
Objectives:
Develop a functional assay of zebrafish (Danio rerio) swimming behavior correlated with anatomic studies of hair cells along the lateral line as a platform for high-throughput drug development against hearing loss.
Methods:
In vivo animal study at university animal care facilities. Five-day postfertilization (dpf) zebrafish were treated with 0 (control)-1000 µM concentrations of cisplatin. In darkness, swimming behavior was analyzed using infrared video systems housed within a novel, multilane, high throughput apparatus to calculate the rheotaxis index (RI). The RI, which represents the ability of fish to properly orient relative to water current, allowed direct comparison of various cisplatin doses to controls simultaneously. Hair cells of zebrafish exposed to cisplatin were also stained with Yo-Pro1 and imaged using confocal microscopy in order to correlate anatomic changes with changes in swimming behavior.
Results:
A dose-dependent relationship between cisplatin concentration and RI was found. 0 µM (control): RI 39.85%; 250 µM: RI 38.11%; 500 µM: RI 25.12%; 750 µM: RI 22.97%; 1000 µM: RI 17.84%. The decline in rheotaxis performance correlated directly with increasing dosage of cisplatin.
Conclusions:
There are currently no Food and Drug Administration–approved pharmacological treatments for hearing loss. Using a validated behavioral assay to test ototoxic dose of cisplatin against varying concentrations of potentially otoprotective/otoregenerative compounds establishes a first-ever, high-throughput biologic platform for drug development against hearing loss.
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