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

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 lo...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2023-10, Vol.12 (21), p.2540
Main Authors: Taler, Kineret, Zatari, Nour, Lone, Mohammad Iqbal, Rotem-Bamberger, Shahar, Inbal, Adi
Format: Article
Language:English
Subjects:
Animals
Antibodies
Capsule Opacification - prevention & control
Cataract
Cataracts
Cell proliferation
Danio rerio
Drug development
Embryos
Epithelial cells
Epithelium
Genetic aspects
Genotype & phenotype
Growth factors
Health aspects
Histology
Lens Capsule, Crystalline - pathology
Lens, Crystalline
Libraries
Lysyl hydroxylase 3
Medical research
Molecular modelling
Mutants
Mutation (Biology)
Phenotypes
plod3
posterior capsular opacification
Prevention
small molecule screen
Sucrose
Surgery
Zebrafish
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Summary: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 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 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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells12212540