PUBLICATION

Identification of Small Molecules for Prevention of Lens Epithelium-Derived Cataract Using Zebrafish

Authors
Taler, K., Zatari, N., Lone, M.I., Rotem-Bamberger, S., Inbal, A.
ID
ZDB-PUB-231111-3
Date
2023
Source
Cells   12(21): (Journal)
Registered Authors
Keywords
4-PBA, Erlotinib, Lysyl hydroxylase 3, cataract, plod3, posterior capsular opacification, small molecule screen, zebrafish
MeSH Terms
  • Animals
  • Capsule Opacification*/prevention & control
  • Epithelium
  • Lens Capsule, Crystalline*/pathology
  • Lens, Crystalline*
  • Zebrafish
PubMed
37947618 Full text @ Cells
Abstract
Cataract is the leading cause of blindness worldwide. It can be treated by surgery, whereby the damaged crystalline lens is replaced by a synthetic lens. Although cataract surgery is highly effective, a relatively common complication named posterior capsular opacification (PCO) leads to secondary loss of vision. PCO is caused by abnormal proliferation and migration of residual lens epithelial cells (LECs) that were not removed during the surgery, which results in interruption to the passage of light. Despite technical improvements to the surgery, this complication has not been eradicated. Efforts are being made to identify drugs that can be applied post-surgery, to inhibit PCO development. Towards the goal of identifying such drugs, we used zebrafish embryos homozygous for a mutation in plod3 that develop a lens phenotype with characteristics of PCO. Using both biased and unbiased approaches, we identified small molecules that can block the lens phenotype of the mutants. Our findings confirm the relevance of zebrafish plod3 mutants' lens phenotype as a model for lens epithelium-derived cataract and add to our understanding of the molecular mechanisms that contribute to the development of this pathology. This understanding should help in the development of strategies for PCO prevention.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping