PUBLICATION
Zebrafish: An In Vivo Screening Model to Study Ocular Phenotypes
- Authors
- Quint, W.H., Tadema, K.C.D., Crins, J.H.C., Kokke, N.C.C.J., Meester-Smoor, M.A., Willemsen, R., Klaver, C.C.W., Iglesias, A.I.
- ID
- ZDB-PUB-220315-30
- Date
- 2022
- Source
- Translational vision science & technology 11: 17 (Journal)
- Registered Authors
- Iglesias, Adriana
- Keywords
- none
- MeSH Terms
-
- Animals
- Disease Models, Animal
- Ectopia Lentis*/genetics
- Eye
- Fibrillin-1/genetics
- Humans
- Phenotype
- Serine Proteases/genetics
- Zebrafish*/genetics
- PubMed
- 35285860 Full text @ Transl Vis Sci Technol
Citation
Quint, W.H., Tadema, K.C.D., Crins, J.H.C., Kokke, N.C.C.J., Meester-Smoor, M.A., Willemsen, R., Klaver, C.C.W., Iglesias, A.I. (2022) Zebrafish: An In Vivo Screening Model to Study Ocular Phenotypes. Translational vision science & technology. 11:17.
Abstract
Purpose To establish a set of assays that allow the in vivo screening of candidate genes for ocular diseases in zebrafish, with an emphasis on refractive error.
Methods Our pipeline includes the most relevant ocular screening measurements to assess (1) ocular biometry using spectral domain optical coherence tomography, (2) refractive status using an eccentric photorefractor, (3) intraocular pressure by tonometry, and (4) optokinetic response to study visual capability in zebrafish. To validate our pipeline and to demonstrate the potential of zebrafish as a valid animal model, we chose two well-characterized genes with an ocular phenotype (PRSS56 and FBN1) and generated two mutant zebrafish lines (prss56 and fbn1). Mutant fish were assessed at 2, 4, and 6 months after fertilization.
Results With the proposed phenotyping pipeline, we showed that ocular biometry, refractive status, intraocular pressure, and visual function can be studied in zebrafish. In the prss56 mutant, the pipeline revealed a dramatic decrease in axial length, mainly owing to a decreased vitreous chamber depth, whereas in the fbn1 mutant, ectopia lentis was the most distinctive ocular phenotype observed. Tonometry in both mutant lines showed an increase in intraocular pressure.
Conclusions The proposed pipeline was applied successfully in zebrafish and can be used for future genetic screenings of candidate genes. While validating our pipeline, we found a close resemblance between the ocular manifestations in the zebrafish mutants and patients harboring mutations in PRSS56 and FBN1. Our results support the validity of our pipeline and highlight the potential of zebrafish as an animal model for in vivo screening of candidate genes for ocular diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping