Catalase and peroxiredoxin 5 protect Xenopus embryos against alcohol-induced ocular anomalies

Author: Peng, Y.; Yang, P.-H.; Guo, Y.; Ng, S.S.M.; Liu, J.; Fung, P.C.W.; Tay, D.; Ge, J.; He, M.-L.; Kung, H.-F.; Lin, M.C.

Description: PURPOSE: To study the molecular mechanisms underlying alcohol-induced ocular anomalies in Xenopus embryos.

METHODS: Xenopus embryos were exposed to various concentrations (0.1%-0.5%) of alcohol, and the subsequent effects in eye development and in eye marker gene expression were determined. To investigate the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in fetal alcohol syndrome (FAS)-associated ocular injury, two antioxidant enzymes, catalase and peroxiredoxin 5, were overexpressed in the two blastomeres of the two-cell stage Xenopus embryos.

RESULTS: Exposure of Xenopus embryos to alcohol during eye development produced marked gross ocular anomalies, including microphthalmia, incomplete closure of the choroid fissure, and malformation of the retina in 40% of the eyes examined. In parallel, alcohol (0.1%-0.5%) dose dependently and significantly reduced the expression of several eye marker genes, of which TBX5, VAX2, and Pax6 were the most vulnerable. Overexpression of catalase and of cytosolic and mitochondrial peroxiredoxin 5 restored the expression of these alcohol-sensitive eye markers and significantly decreased the frequency of ocular malformation from 39% to 21%, 19%, and 13% respectively. All these enzymes reduced alcohol-induced ROS production, but only peroxiredoxin 5 inhibited RNS formation in the alcohol-treated embryos.

CONCLUSIONS: The results suggest that oxidative and nitrosative stresses both contribute to alcohol-induced fetal ocular injury.

Subject headings: Abnormalities, Drug-Induced/etiology/metabolism/prevention & control; Animals; Biomarkers/analysis; Blotting, Western; Catalase/physiology; Choroid/abnormalities; Dose-Response Relationship, Drug; Embryo, Nonmammalian/drug effects; Ethanol/toxicity; Eye Abnormalities/chemically induced/metabolism/prevention & control; Eye Proteins; Homeodomain Proteins/genetics/metabolism; Microphthalmos/chemically induced/metabolism/prevention & control; Oxidative Stress; Paired Box Transcription Factors; Peroxidases/physiology; Peroxiredoxins; Reactive Nitrogen Species/antagonists & inhibitors/metabolism; Reactive Oxygen Species/antagonists & inhibitors/metabolism; Repressor Proteins; Retina/abnormalities; Reverse Transcriptase Polymerase Chain Reaction; T-Box Domain Proteins/genetics/metabolism; Xenopus Proteins; Xenopus laevis/embryology

Publication year: 2004

Journal or book title: Investigative Ophthalmology & Visual Science

Volume: 45

Issue: 1

Pages: 23-29

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Type: Journal Article

Serial number: 1475