Related Experiment Video
Updated: Aug 11, 2025
10:39
Lens Transplantation in Zebrafish and its Application in the Analysis of Eye Mutants
Published on: June 1, 2009
11.1K
Post-GWAS screening of candidate genes for refractive error in mutant zebrafish models
Wim H Quint1,2, Kirke C D Tadema1,2, Nina C C J Kokke1,2
1Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
Scientific Reports
|February 3, 2023
Summary
Genome-wide association studies identified genes linked to refractive errors. Zebrafish models revealed LAMA2, LRRC4C, and KCNQ5 play functional roles in myopia development, offering new research avenues.
Area of Science:
- Genetics
- Ophthalmology
- Developmental Biology
Background:
- Genome-wide association studies (GWAS) have identified numerous genetic loci associated with refractive errors (RE), including myopia.
- However, functional validation and exploration of candidate genes within these loci remain limited, hindering a complete understanding of RE pathogenesis.
- Understanding the genetic basis of refractive errors is crucial for developing effective interventions.
Purpose of the Study:
- To functionally validate candidate genes identified through GWAS for their role in refractive error development.
- To investigate the specific contribution of nine prioritized genes (TJP2, PDE11A, SHISA6, LAMA2, LRRC4C, KCNQ5, GNB3, RBFOX1, and GRIA4) to refractive error.
- To establish zebrafish models for studying the genetic mechanisms underlying myopia.
Main Methods:
- CRISPR/Cas9 gene editing was used to generate knockout zebrafish mutants for nine candidate genes.
- Axial length was measured using spectral-domain optical coherence tomography.
- Refractive status was assessed using eccentric photorefraction at juvenile and adult stages.
- In situ hybridization was performed to determine gene expression patterns in the zebrafish retina.
Main Results:
- Three zebrafish mutants (LAMA2, LRRC4C, and KCNQ5 knockouts) exhibited significantly increased axial length and a myopic shift in refractive status.
- These findings suggest a potential role for the human orthologs of LAMA2, LRRC4C, and KCNQ5 in the development of myopia.
- In situ hybridization confirmed the expression of these three genes throughout the zebrafish retina.
Conclusions:
- The generated zebrafish models provide functional evidence for the involvement of LAMA2, LRRC4C, and KCNQ5 in refractive error development.
- These genes are implicated in the retina-to-sclera signaling pathway crucial for myopia.
- This study offers valuable models for further elucidation of myopia pathogenesis and potential therapeutic targets.
