Development of an experimental model for ocular toxicity screening in Zebrafish

Soonil Koun1, Youngsub Eom2, Mi Jeong Kim3

  • 1Biomedical Research Center, Korea University Ansan Hospital, Gyeonggi-do, Republic of Korea; Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea; Zebrafish Translational Medical Research Center, Korea University, Ansan, Gyeonggi-do, Republic of Korea; Incheon Technopark Bioindustry Center, Incheon, Republic of Korea.

Abstract

Insights

A novel contrast-optomotor response (C-OMR) assay in zebrafish effectively detects visual function changes. This sensitive method can assess drug toxicity and eye diseases by analyzing visual impairment from substances like gentamicin and digoxin.

Area of Science:

  • Neuroscience
  • Ophthalmology
  • Toxicology

Background:

  • Visual function assessment is crucial for understanding ocular health and drug side effects.
  • Traditional optomotor response (OMR) assays have limitations in sensitivity.
  • Zebrafish offer a valuable model for visual function studies due to their optical properties and genetic tractability.

Purpose of the Study:

  • To develop and validate a novel contrast-optomotor response (C-OMR) assay for enhanced visual function assessment in zebrafish.
  • To evaluate the sensitivity of the C-OMR assay in detecting drug-induced visual impairment.
  • To compare the efficacy of the C-OMR assay with the standard OMR assay.

Main Methods:

  • Zebrafish larvae were exposed to varying concentrations of gentamicin and digoxin (0, 5, 10, 15 μM) for 24 hours at four days post-fertilization.
  • The contrast-optomotor response (C-OMR) assay was performed using graded contrast gray-white stripes.
  • Larval swimming behavior was recorded, with success defined as swimming for 30 seconds; results were analyzed across four independent trials.

Main Results:

  • A significant reduction in successful swimming was observed in zebrafish larvae treated with 5, 10, and 15 μM gentamicin and 10 and 15 μM digoxin compared to controls.
  • The C-OMR assay demonstrated dose-dependent effects, distinguishing visual function decreases related to specific concentrations of gentamicin and digoxin.
  • The standard OMR assay with a single contrast stripe failed to differentiate these effects.

Conclusions:

  • The C-OMR assay using graded contrast stripes is more sensitive than the standard OMR assay for evaluating visual function in zebrafish.
  • This enhanced assay holds significant potential for assessing drug toxicity and identifying drug-induced ocular side effects.
  • The C-OMR method can improve the understanding of ocular diseases and aid in clinical drug safety evaluations.

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