Development of an experimental model for ocular toxicity screening in Zebrafish

Background: To investigate the efficacy of a novel experimental model for exploring visual function using a contrast-optomotor response (C-OMR) assay made by applying the contrast sensitivity test to the OMR assay in zebrafish. Methods: Zebrafish larvae were treated with 0 (control), 5, 10, or 15 μM gentamicin and digoxin for 24 h at four days post-fertilization (dpf). Zebrafish larvae were assessed using the C-OMR assay with graded contrast gray-white stripes at 5 dpf, and the results were expressed as the percentage of larvae that finished swimming for 30 s (n = 20 per each group). The same C-OMR assay was repeated four times using different larvae. Results: The percentage of larvae that finished swimming within 30 s was significantly reduced in larvae treated with 5, 10, and 15 μM gentamicin and 10 and 15 μM digoxin as compared to the Control groups. The C-OMR assay could distinguish that the decrease in visual function was different depending on the concentration of gentamicin and digoxin (5, 10, and 15 μM), whereas the OMR test with one contrast gray-white stripe could not. Conclusions: The method of analyzing zebrafish OMR using graded contrast gray-white stripes is more sensitive than the OMR assay alone and may be more useful for assessing the drug toxicity and eye-related diseases to improve the understanding of drug-induced ocular side effects in the clinic.