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Modeling ocular lens disease in Xenopus.

Justine Viet¹, David Reboutier¹, Serge Hardy¹

¹Univ Rennes, CNRS, IGDR-UMR 6290, F-35000, Rennes, France.

Developmental Dynamics : an Official Publication of the American Association of Anatomists

|December 25, 2019

Summary

Xenopus laevis tadpoles offer a novel model for studying cataracts. Gene disruption in tadpoles revealed lens defects similar to human cataracts, suggesting potential for new treatment screening.

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Area of Science:

Developmental biology
Ophthalmology
Genetics

Background:

Cataracts, or ocular lens clouding, are classified as congenital or age-related.
Developing novel cataract treatments necessitates innovative research models.
The potential of Xenopus embryos as a cataract model has not been previously explored.

Purpose of the Study:

To characterize lens development in Xenopus laevis.
To investigate the role of specific genes in lens formation and cataract development.
To evaluate Xenopus as a model for studying congenital cataracts and screening potential treatments.

Main Methods:

Lens formation was characterized in Xenopus laevis tailbuds and tadpoles.
CRISPR/Cas9 was used to disrupt orthologues of three mammalian cataract-linked genes (pax6, gja8, dnase2b).

Keywords:

CRISPR DNASE2B GJA8 PAX6 cataract pathology

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Consequences of gene inactivation were assessed via external examination, histochemical analyses, and functional vision assays.

Main Results:

Disruption of pax6 resulted in severe eye developmental defects.
Inactivation of gja8 and dnase2b led to lens defects mirroring human cataracts, including impaired vision, retained nuclei in lens fiber cells, and actin fiber disorganization.
Treatment with 4-phenylbutyrate showed potential for improving visual acuity in gja8 mutant tadpoles.

Conclusions:

Xenopus laevis serves as a valuable model organism for understanding the molecular pathology of congenital eye defects, specifically cataracts.
This model system facilitates the screening of molecules for their potential to prevent or reverse cataract formation.
The study highlights the utility of Xenopus in ophthalmological research and drug discovery for vision disorders.