Project description:Analysis of gene expression changes in galactose-induced cataracts when an Atm inhibitors is added. A total of six samples were analyzed: a sample without induced turbidity (control), three samples in which turbidity was induced by galactose (galactose), and a sample with ATM inhibitor added (KU55933 or AZD0156).
Project description:We investigated the therapeutic effects of histone acetyltransferase (HAT) inhibitors on cataracts using an ex vivo model of galactose-induced cataracts in the rat lens.Among the tested HAT inhibitors, TH1834 was the only inhibitor that could completely reverse white opacities once formed in the lens. Combination treatment with C646/CPTH2 and CBP30/CPTH2 also had therapeutic effects. To identify the genes regulated by HAT inhibitors, we conducted microarray analysis of treated and untreated cataract samples.
Project description:The Shumiya cataract rat (SCR) is a model for hereditary cataract. Two-third of these rats develop lens opacity within 10-11-weeks. Onset of cataract is attributed to the synergetic effect of lanosterol synthase (Lss) and farnesyl-diphosphate farnesyltransferase 1 (Fdft1) mutant alleles that lead to cholesterol deficiency in the lenses, which in turn adversely affects lens biology including the growth and differentiation of lens epithelial cells (LECs). Nevertheless, the molecular events and changes in gene expression associated with the onset of lens opacity in SCR is poorly understood. Our study aimed to identify the gene expression patterns during cataract formation in SCRs, which may be responsible for cataractogenesis in SCR.
Project description:The addition of Pyruvate to the lens induced by galactose eliminated the white clouding formed and showed a therapeutic effect. Genes regulated by pyruvate addition were identified by microarray analysis. A total of seven samples were used in this analysis: two samples without galactose (control), three samples with galactose (galactose) and two samples with Pyruvate (Pyruvate).
Project description: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.
Project description:We applied previously established in silico whole-embryo body (WB)-subtraction-based approach to identify “lens-enriched” genes. These new RNA-seq datasets on embryonic stages E10.5, E12.5, E14.5 and E16.5 confirmed high expression of established cataract-linked genes and identified several new potential regulators in the lens. Finally, we present lens stage-specific UCSC Genome Brower annotation-tracks; these are publicly accessible through iSyTE (https://research.bioinformatics.udel.edu/iSyTE/) and enable a user-friendly visualization of lens gene expression/enrichment to help prioritize genes from high-throughput data from cataract cases.
Project description:Early changes in the transcriptome associated with lens wounding in an ex vivo post-cataract surgery chicken model. Here we report the changes in the transcriptome that occur 1hr vs. time 0 post-cataract surgery wounding. Our data provide a molecular framework for understanding the early gene changes associated with the injury response of the lens.
Project description:To explore the regulatory mechanism of age-related cataract (ARC) formation and progression,we construct sodium selenite-induced rat cataract model and performed the high-throughput RNA sequencing (HTS) technology to identify the mRNA and miRNA expression profiles of the lens from Na2Se03-induced and saline - injected Sprague Dawley rats.
Project description:To explore the regulatory mechanism of age-related cataract (ARC) formation and progression,we construct sodium selenite-induced rat cataract model and performed the high-throughput RNA sequencing (HTS) technology to identify the mRNA and miRNA expression profiles of the lens from Na2Se03-induced and saline - injected Sprague Dawley rats.
Project description:This trancriptome analysis reveals the first detailed analysis on how the remnant lens epithelial cells (LECs) greatly reprogram their transcriptome towards inflammation/fibrosis by 24 hours post cataract surgery (PCS).