Early safety assessment of human oculotoxic drugs using the zebrafish visualmotor response

Sudhakar Deeti1, Sean O'Farrell1, Breandán N Kennedy1

  • 1UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.

Abstract

Insights

This study shows that a semi-automated visual behavior assay in zebrafish larvae can effectively predict drug-induced ocular toxicity. The visual motor response (VMR) assay demonstrated high sensitivity and specificity for identifying adverse ocular effects.

Area of Science:

  • Ophthalmology
  • Toxicology
  • Neuroscience

Background:

  • Prescription drugs can cause ocular damage, affecting visual pathways and retinal function.
  • Zebrafish larvae offer a promising model for pre-clinical prediction of drug-induced ocular toxicity.
  • Semi-automated visual behavior assays can enhance the efficiency of these predictions.

Purpose of the Study:

  • To evaluate a semi-automated visual behavior assay for predicting drug-induced ocular toxicity in zebrafish.
  • To assess the sensitivity and specificity of the visual motor response (VMR) assay in detecting adverse ocular effects.

Main Methods:

  • Larvae were exposed to known oculotoxic and control drugs.
  • Assessed visual behavior using visual motor response (VMR), optokinetic response (OKR), and touch response assays.
  • Quantified locomotor and eye responses to light changes and visual stimuli.

Main Results:

  • Five of six known oculotoxic drugs demonstrated adverse effects on zebrafish visual behavior.
  • The VMR assay showed high predictive accuracy with 83% sensitivity and 100% specificity.
  • No significant morphological changes or general locomotor differences were observed in treated larvae.

Conclusions:

  • The visual motor response (VMR) assay is a suitable and predictive pre-clinical method for evaluating drug-induced ocular toxicity.
  • This approach efficiently assesses adverse effects on visual function in vivo.
  • The VMR assay provides a reliable tool for early-stage drug safety assessment.

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