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Atm inhibition decreases lens opacity in a rat model of galactose-induced cataract
by
Nagaya, Masaya
, Oki, Masaya
, Takamura, Yoshihiro
, Inatani, Masaru
, Takashima, Masaru
, Kanada, Fumito
in
Actin
/ Actins - metabolism
/ Analysis
/ Animals
/ Apoptosis
/ Ataxia
/ Ataxia telangiectasia
/ Ataxia telangiectasia mutated protein
/ Ataxia Telangiectasia Mutated Proteins - genetics
/ Biology and Life Sciences
/ Blindness - complications
/ Care and treatment
/ Cataract
/ Cataract - chemically induced
/ Cataract - genetics
/ Cataracts
/ Cell cycle
/ Cell differentiation
/ Diabetes
/ Diagnosis
/ DNA damage
/ DNA microarrays
/ Engineering and Technology
/ Epithelial cells
/ Epithelium
/ Experiments
/ Galactose
/ Galactose - metabolism
/ Gene expression
/ Genes
/ Health aspects
/ Inhibitors
/ Kinases
/ Lens, Crystalline - metabolism
/ Lenses
/ Medicine and Health Sciences
/ Mesenchyme
/ Molecular modelling
/ mRNA
/ Opacity
/ Oxidative stress
/ Physical Sciences
/ Protein binding
/ Rats
/ Regulatory mechanisms (biology)
/ Research and Analysis Methods
/ RNA, Messenger - metabolism
/ Rodents
/ Therapeutic targets
2022
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Atm inhibition decreases lens opacity in a rat model of galactose-induced cataract
by
Nagaya, Masaya
, Oki, Masaya
, Takamura, Yoshihiro
, Inatani, Masaru
, Takashima, Masaru
, Kanada, Fumito
in
Actin
/ Actins - metabolism
/ Analysis
/ Animals
/ Apoptosis
/ Ataxia
/ Ataxia telangiectasia
/ Ataxia telangiectasia mutated protein
/ Ataxia Telangiectasia Mutated Proteins - genetics
/ Biology and Life Sciences
/ Blindness - complications
/ Care and treatment
/ Cataract
/ Cataract - chemically induced
/ Cataract - genetics
/ Cataracts
/ Cell cycle
/ Cell differentiation
/ Diabetes
/ Diagnosis
/ DNA damage
/ DNA microarrays
/ Engineering and Technology
/ Epithelial cells
/ Epithelium
/ Experiments
/ Galactose
/ Galactose - metabolism
/ Gene expression
/ Genes
/ Health aspects
/ Inhibitors
/ Kinases
/ Lens, Crystalline - metabolism
/ Lenses
/ Medicine and Health Sciences
/ Mesenchyme
/ Molecular modelling
/ mRNA
/ Opacity
/ Oxidative stress
/ Physical Sciences
/ Protein binding
/ Rats
/ Regulatory mechanisms (biology)
/ Research and Analysis Methods
/ RNA, Messenger - metabolism
/ Rodents
/ Therapeutic targets
2022
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Atm inhibition decreases lens opacity in a rat model of galactose-induced cataract
by
Nagaya, Masaya
, Oki, Masaya
, Takamura, Yoshihiro
, Inatani, Masaru
, Takashima, Masaru
, Kanada, Fumito
in
Actin
/ Actins - metabolism
/ Analysis
/ Animals
/ Apoptosis
/ Ataxia
/ Ataxia telangiectasia
/ Ataxia telangiectasia mutated protein
/ Ataxia Telangiectasia Mutated Proteins - genetics
/ Biology and Life Sciences
/ Blindness - complications
/ Care and treatment
/ Cataract
/ Cataract - chemically induced
/ Cataract - genetics
/ Cataracts
/ Cell cycle
/ Cell differentiation
/ Diabetes
/ Diagnosis
/ DNA damage
/ DNA microarrays
/ Engineering and Technology
/ Epithelial cells
/ Epithelium
/ Experiments
/ Galactose
/ Galactose - metabolism
/ Gene expression
/ Genes
/ Health aspects
/ Inhibitors
/ Kinases
/ Lens, Crystalline - metabolism
/ Lenses
/ Medicine and Health Sciences
/ Mesenchyme
/ Molecular modelling
/ mRNA
/ Opacity
/ Oxidative stress
/ Physical Sciences
/ Protein binding
/ Rats
/ Regulatory mechanisms (biology)
/ Research and Analysis Methods
/ RNA, Messenger - metabolism
/ Rodents
/ Therapeutic targets
2022
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Atm inhibition decreases lens opacity in a rat model of galactose-induced cataract
Journal Article
Atm inhibition decreases lens opacity in a rat model of galactose-induced cataract
2022
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Overview
Cataract causes vision loss and blindness due to formation of opacities of the lens. The regulatory mechanisms of cataract formation and progression remain unclear, and no effective drug treatments are clinically available. In the present study, we tested the effect of ataxia telangiectasia mutated (Atm) inhibitors using an ex vivo model in which rat lenses were cultured in galactose-containing medium to induce opacity formation. After lens opacities were induced by galactose, the lenses were further incubated with the Atm inhibitors AZD0156 or KU55933, which decreased lens opacity. Subsequently, we used microarray analysis to investigate the underlying molecular mechanisms of action, and extracted genes that were upregulated by galactose-induced opacity, but not by inhibitor treatment. Quantitative measurement of mRNA levels and subsequent STRING analysis revealed that a functional network consisting primarily of actin family and actin-binding proteins was upregulated by galactose treatment and downregulated by both Atm inhibitors. In particular, Acta2 is a known marker of epithelial-mesenchymal transition (EMT) in epithelial cells, and other genes connected in this functional network ( Actn1 , Tagln , Thbs1 , and Angptl4 ) also suggested involvement of EMT. Abnormal differentiation of lens epithelial cells via EMT could contribute to formation of opacities; therefore, suppression of these genes by Atm inhibition is a potential therapeutic target for reducing opacities and alleviating cataract-related visual impairment.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Analysis
/ Animals
/ Ataxia
/ Ataxia telangiectasia mutated protein
/ Ataxia Telangiectasia Mutated Proteins - genetics
/ Cataract
/ Cataract - chemically induced
/ Diabetes
/ Genes
/ Kinases
/ Lens, Crystalline - metabolism
/ Lenses
/ Medicine and Health Sciences
/ mRNA
/ Opacity
/ Rats
/ Regulatory mechanisms (biology)
/ Research and Analysis Methods
/ Rodents
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