title: Genetic Variation Shapes Visual-Motor Behavior: Insights from High-Throughput Optomotor Response Screening in Medaka Inbred Population
creator: Suzuki, Risa
description: Congenital eye diseases (CEDs) have been associated with monogenic mutations, yet the variability in clinical severity among individuals indicates a strong polygenic component.   The underlying gene-gene and gene-environment interactions causing this variability have so far been largely unexplored, owing to the inherent challenges of disentangling such interactions in human populations and the substantial sample sizes required to achieve statistical power in animal models. In this study, I made use of the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel, a collection of genetically and phenotypically diverse inbred strains of the Japanese rice fish medaka (Oryzias latipes and Oryzias sakaizumi) derived from a wild population. To dissect the genetic architecture underlying eye development and disease, I combined this resource with high-throughput behavioral phenotyping, using visuomotor behavior as a functional readout of visual system integrity.    To this end, I developed two high-throughput optomotor response (OMR) assays with an automated analysis pipeline to measure visual acuity, color and contrast sensitivity simultaneously, in 15 to 50 hatchlings at a time. Using this setup I demonstrated that visuomotor responses vary across albino mutant, inbred strains of medaka, and zebrafish, with the albino mutant exhibiting enhanced spatial, color and contrast sensitivity.   By optimizing light-induced retinal degeneration setup I successfully established, for the first time, a model of light-induced retinal degeneration in medaka hatchling, providing a novel model for investigating CEDs mechanisms. Moreover I showed that susceptibility to retinal damage varied across medaka strains and medaka in general is more resistant to retinal degeneration induced by the light than zebrafish.   A comparison of visual sensitivity and a spectrum of behavioral phenotypes (e.g. visual acuity, speed adjustment, and total distance traveled), showed great differences between the 76 tested inbred stains. Furthermore I performed functional assessments of retina in selected strains, including optokinetic response (OKR), electroretinography (ERG), and eye morphology analysis, which partially aligned with the OMR data and provided complementary evidence of visual impairments.  To uncover the genetic basis of these complex traits, I utilized strategic crosses between seven phenotypically contrasting MIKK strains and phenotyped the F2 generation. A genome-wide linkage analysis using F2 segregation has led to the identification of five quantitative trait loci (QTLs) associated with distinct visual and behavioral traits.     This work demonstrates that the automated OMR platform developed in this study can efficiently identify QTLs linked mechanisms involved in eye development, visual processing, and visuomotor integration and thereby setting the foundation to uncovering the network of causative genes contributing to the variability in congenital eye diseases.  It provides a robust framework for future studies aimed at dissecting gene-gene and gene-environment interactions, ultimately contributing to our understanding of the genetic and environmental factors driving variability in congenital eye diseases.
date: 2025
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserver/37319/1/Risa_PhD_thesis_full_ver.2%20%284%29.pdf
identifier: DOI:10.11588/heidok.00037319
identifier: urn:nbn:de:bsz:16-heidok-373197
identifier:   Suzuki, Risa  (2025) Genetic Variation Shapes Visual-Motor Behavior: Insights from High-Throughput Optomotor Response Screening in Medaka Inbred Population.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/37319/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng