Transcriptome of the GSH-Depleted Lens Reveals Changes in Detoxification and EMT Signaling Genes, Transport Systems, and Lipid Homeostasis

Investigative Ophthalmology & Visual Science
Jeremy A WhitsonXingjun Fan

Abstract

To understand the effects of glutathione (GSH)-deficiency on genetic processes that regulate lens homeostasis and prevent cataractogenesis. 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. 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...Continue Reading

Citations

Feb 18, 2018·Nature Communications·Wei HuangYigang Wang
Jan 15, 2021·Antioxidants·Ana Álvarez-BarriosHéctor González-Iglesias
Mar 17, 2021·Free Radical Biology & Medicine·Zongbo WeiXingjun Fan
Sep 26, 2020·Progress in Retinal and Eye Research·I M WormstoneJ A Eldred
Aug 3, 2021·Experimental Eye Research·Tayler F L WishartFrank J Lovicu
Aug 24, 2021·The Ocular Surface·Brian ThompsonVasilis Vasiliou

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Datasets Mentioned

BETA
GSE95688

Methods Mentioned

BETA
PCR
chip
RNA-seq
Assay
ELISA

Software Mentioned

Reactome
BLAST
Primer
Illumina
IPA

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