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Rat ex vivo cataract model using DNA damage inducer

ABSTRACT: Rat ex vivo cataract model using DNA damage inducer

PROVIDER: PRJNA800268 | ENA |

REPOSITORIES: ENA

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Rat ex vivo cataract model using DNA damage inducer

Project description:By adding MMS or Bleomycin, a DNA damage inducing agent, to the removed rat lens and culturing it, opacity was formed in the lens. To investigate genes whose expression fluctuates when DNA damage is inflicted and causes lens opacity, microarray analysis was performed.

2022-08-11 | GSE194317 | GEO

Analysis of cataract-regulated genes using chemical DNA damage induction in a rat ex vivo model.

Project description:Although cataracts affect almost all people at advanced age and carry a risk of blindness, the mechanisms of cataract development remain incompletely understood. Oxidative stress, which is a causative factor in cataract, results in DNA breakage, which suggests that DNA damage could contribute to the formation of cataracts. We developed an ex vivo experimental system to study changes in gene expression during the formation of opacities in the lens by culturing explanted rat lenses with Methylmethanesulfonate (MMS) or Bleomycin, which induce DNA damage. Lenses cultured using this experimental system developed cortical opacity, which increased in a concentration- and time-dependent manner. In addition, we compared expression profiles at the whole gene level using microarray analysis of lenses subjected to MMS or Bleomycin stress. Microarray findings in MMS-induced opacity were validated and gene expression was measured from Days 1-4 using RT-qPCR. Altered genes were classified into four groups based on the days of peak gene expression: Group 1, in which expression peaked on Day 1; Group 2, in which expression peaked on Day 2; Group 3, in which expression progressively increased from Days 1-4 or were upregulated on Day 1 and sustained through Day 4; and Group 4, in which expression level oscillated from Days 1-4. Genes involved in lipid metabolism were restricted to Group 1. DNA repair- and cell cycle-related genes were restricted to Groups 1 and 2. Genes associated with oxidative stress and drug efflux were restricted to Group 2. These findings suggest that in temporal changes of MMS-induced opacity formation, the activated pathways could occur in the following order: lipid metabolism, DNA repair and cell cycle, and oxidative stress and drug efflux.

| S-EPMC9728860 | biostudies-literature

Transcriptome changes with GSK-J4 treatment in an ex vivo post-cataract surgery model

Project description:Transcriptome changes with GSK-J4 treatment in an ex vivo post-cataract surgery model

| PRJNA880913 | ENA

Changes in gene expression time 0 vs. 1hr post-cataract sugery wounding in the lens

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.

2023-11-04 | GSE239368 | GEO

Characterization of N6-Methyladenosine lncRNAs in sporadic congenital cataract and age-related cataract

Project description:To characterize the N6-methyladenosine (m6A) modification patterns in long non-coding RNAs (lncRNAs) in sporadic congenital cataract (CC) and age-related cataract(ARC).

2024-11-06 | GSE221970 | GEO

Expression data from lens epithelial cells (LECs) from Shumiya cataract rats (SCR) with or without cataract (Cat+ or Cat-)

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.

2020-07-31 | GSE152616 | GEO

Therapeutic Effect of Histone Acetyltransferase Inhibitors on Galactose-Induced Cataract in Rats

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.

2022-12-11 | GSE186248 | GEO

Transcriptome sequencing and microRNA–mRNA regulatory network construction in the lens from a Na2Se03-induced Sprague Dawley rat cataract model [RNA]

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.

2023-11-22 | GSE226273 | GEO

Transcriptome sequencing and microRNA–mRNA regulatory network construction in the lens from a Na2Se03-induced Sprague Dawley rat cataract model [miRNA]

2023-11-22 | GSE226272 | GEO

Rosmarinic Acid Restores Complete Transparency of Sonicated Human Cataract Ex Vivo and Delays Cataract Formation In Vivo.

Project description:Cataract, the leading cause of vision impairment worldwide, arises from abnormal aggregation of crystallin lens proteins. Presently, surgical removal is the only therapeutic approach. Recent findings have triggered renewed interest in development of non-surgical treatment alternatives. However, emerging treatments are yet to achieve full and consistent lens clearance. Here, the first ex vivo assay to screen for drug candidates that reduce human lenticular protein aggregation was developed. This assay allowed the identification of two leading compounds as facilitating the restoration of nearly-complete transparency of phacoemulsified cataractous preparation ex vivo. Mechanistic studies demonstrated that both compounds reduce cataract microparticle size and modify their amyloid-like features. In vivo studies confirmed that the lead compound, rosmarinic acid, delays cataract formation and reduces the severity of lens opacification in model rats. Thus, the ex vivo assay may provide an initial platform for broad screening of potential novel therapeutic agents towards pharmacological treatment of cataract.

| S-EPMC6008418 | biostudies-literature

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