ArticleInvestigative ophthalmology & visual science2017
Transcriptome of the GSH-Depleted Lens Reveals Changes in Detoxification and EMT Signaling Genes, Transport Systems, and Lipid Homeostasis.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Transcriptome Meta-Analysis Uncovers Cell-Specific Regulatory Relationships in Embryonic, Juvenile, Adult, and Aged Mouse Lens Epithelium and Fibers.Investigative ophthalmology & visual science · 2025Pooled it
- RNA-binding proteins in the mouse lens: Functional classifications, expression profiling, and interaction studies of Carhsp1 with crystallin mRNAs.Developmental biology · 2026Article
- Transcriptomic-Driven Drug Repurposing Reveals SP600125 as a Promising Drug Candidate for the Treatment of Glial-Mesenchymal Transition in Glioblastoma.International journal of molecular sciences · 2025Article
- Transcriptomic Analysis of Human Lens Epithelium Tissue With and Without Cataract Surgery: Uncovering Novel Pathways of Post-Surgical Lens Epithelium Remodeling.Investigative ophthalmology & visual science · 2025Article
- Unanswered questions regarding the pathogenesis of late onset posterior capsular opacification.Frontiers in ophthalmology · 2025Review
- Deficiency in glutathione peroxidase 4 (GPX4) results in abnormal lens development and newborn cataract.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Oxidative Stress in Cataract Formation: Is There a Treatment Approach on the Horizon?Antioxidants (Basel, Switzerland) · 2024Review
- Redox Regulation in Age-Related Cataracts: Roles for Glutathione, Vitamin C, and the NRF2 Signaling Pathway.Nutrients · 2023Review
- Oxidative stress-induced temporal activation of ERK1/2 phosphorylates coreceptor of Wnt/β-catenin for myofibroblast formation in human lens epithelial cells.Molecular vision · 2023Article
- Article
- MYPT1/PP1-Mediated EZH2 Dephosphorylation at S21 Promotes Epithelial-Mesenchymal Transition in Fibrosis through Control of Multiple Families of Genes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues.Chemico-biological interactions · 2022Article
- RNA-Seq analysis in giant pandas reveals the differential expression of multiple genes involved in cataract formation.BMC genomic data · 2021Article
- Impaired GSH biosynthesis disrupts eye development, lens morphogenesis and PAX6 function.The ocular surface · 2021Article
- A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis.BMC genomics · 2021Article
- Aging lens epithelium is susceptible to ferroptosis.Free radical biology & medicine · 2021Article
- Antioxidant Defenses in the Human Eye: A Focus on Metallothioneins.Antioxidants (Basel, Switzerland) · 2021Review
- MS/MS in silico subtraction-based proteomic profiling as an approach to facilitate disease gene discovery: application to lens development and cataract.Human genetics · 2020Article
- Histone acetyltransferase and Polo-like kinase 3 inhibitors prevent rat galactose-induced cataract.Scientific reports · 2019Article
- Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration.Nature communications · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Purpose: To understand the effects of glutathione (GSH)-deficiency on genetic processes that regulate lens homeostasis and prevent cataractogenesis. Methods: The transcriptome of lens epithelia and fiber cells was obtained from C57BL/6 LEGSKO (lens GSH-synthesis knockout) and buthionine sulfoximine (BSO)-treated LEGSKO mice and compared to C57BL/6 wild-type mice using RNA-Seq. Transcriptomic data were confirmed by qPCR and Western blot/ELISA on a subset of genes. Results: RNA-Seq results were in excellent agreement with qPCR (correlation coefficients 0.87-0.94 and P < 5E-6 for a subset of 36 mRNAs). Of 24,415 transcripts mapped to the mouse genome, 441 genes showed significantly modulated expression. Pathway analysis indicated major changes in epithelial-mesenchymal transition (EMT) signaling, visual cycle, small molecule biochemistry, and lipid metabolism. GSH-deficient lenses showed upregulation of detoxification genes, including Aldh1a1, Aldh3a1 (aldehyde dehydrogenases), Mt1, Mt2 (metallothioneins), Ces1g (carboxylesterase), and Slc14a1 (urea transporter UT-B). Genes in canonical EMT pathways, including Wnt10a, showed upregulation in lens epithelia samples. Severely GSH-deficient lens epithelia showed downregulation of vision-related genes (including crystallins). The BSO-treated LEGSKO lens epithelia transcriptome has significant correlation (r = 0.63, P < 0.005) to that of lens epithelia undergoing EMT. Protein expression data correlated with transcriptomic data and confirmed EMT signaling activation. Conclusions: These results show that GSH-deficiency in the lens leads to expression of detoxifying genes and activation of EMT signaling, in addition to changes in transport systems and lipid homeostasis. These data provide insight into the adaptation and consequences of GSH-deficiency in the lens and suggest that GSH plays an important role in lenticular EMT pathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.