Investigating the Mechanisms Underlying Drug-Induced Retinotoxicity (360G-Wellcome-207227_Z_17_Z)

Summary: Quinoline-based compounds have been reported to cause forms of retinal dystrophy across a range of species (e.g. chloroquine-induced Bull’s Eye Maculopathy in humans, fluoroquinolone-induced retinal degeneration in cats, quinine-induced retinotoxicity in zebrafish). The precise mechanism underlying this form of retinal degeneration/toxicity is unknown. Here we will use a zebrafish drug-treated model to examine the precise effect of quinoline toxicity on retinal histology and retinal pathways. For this study we will examine quinine, fluoroquine, chloroquine and a novel quinoline compound. Aim: To use an induced zebrafish model to facilitate understanding of the cellular and molecular basis underpinning quinoline-induced retinotoxicity Goal 1. Determine drug dose which induces retinotoxicity Drug treat larval zebrafish and examine visual function using two visual behaviour assays: optokinetic response and semi-automated optomotor response (equipment available in the Zebrafish Facility). Goal 2. Investigate whether retinotoxicity affects retinal histology Drug-treat larval zebrafish and compare retinal histology to vehicle treated controls using fluorescent microscopy. Goal 3. Investigate whether retinotoxicity affects the expression of genes involved in visual function Compare the expression of genes involved in visual function in drug and vehicle treated zebrafish. This project will assist understanding of the cellular and molecular basis underpinning quinoline-induced retinotoxicity