Zebrafish: An In Vivo Screening Model to Study Ocular Phenotypes

Area of Science:

• Ophthalmology
• Genetics
• Zebrafish Model Organisms

Background:

• Ocular diseases represent a significant global health burden.
• Genetic factors play a crucial role in the etiology of many eye conditions.
• Zebrafish offer a powerful model for genetic screening due to their optical properties and genetic tractability.

Purpose of the Study:

• To develop and validate a comprehensive in vivo screening pipeline for candidate genes associated with ocular diseases in zebrafish.
• To focus on refractive error as a key phenotype for screening.
• To establish a robust platform for identifying genetic causes of eye conditions.

Main Methods:

• Established a phenotyping pipeline incorporating ocular biometry (spectral domain optical coherence tomography), refractive status (eccentric photorefractor), intraocular pressure (tonometry), and visual function (optokinetic response).
• Generated and analyzed two zebrafish mutant lines (prss56 and fbn1) with known ocular phenotypes.
• Assessed mutant fish at multiple time points (2, 4, and 6 months post-fertilization).

Main Results:

• The pipeline successfully quantified ocular biometry, refractive status, intraocular pressure, and visual function in zebrafish.
• prss56 mutants exhibited reduced axial length and vitreous chamber depth.
• fbn1 mutants displayed ectopia lentis, and both mutants showed increased intraocular pressure.
• Zebrafish mutant phenotypes closely mirrored human conditions linked to PRSS56 and FBN1 mutations.

Conclusions:

• The developed zebrafish phenotyping pipeline is effective for in vivo genetic screening of ocular disease candidate genes.
• Zebrafish serve as a valuable animal model for studying the genetic basis of human ocular diseases, including refractive error.
• The pipeline's successful validation with known genes underscores its potential for future discovery in ophthalmology research.