In-depth transcriptomic analyses investigating molecular mechanisms underlying diabetic retinopathy
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ABSTRACT:
PROVIDER: PRJNA672925 | ENA |
REPOSITORIES: ENA
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Project description:In-depth transcriptomic analyses investigating molecular mechanisms underlying diabetic retinopathy (totalRNA)
| PRJNA672928 | ENA
Project description:In-depth transcriptomic analyses investigating molecular mechanisms underlying diabetic retinopathy (smallRNA)
| PRJNA672929 | ENA
Project description:Diabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Here we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 80 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP−PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. Our findings offer an unprecedented insight into the development of DR and provide potential avenues for future therapeutic intervention.
2021-04-19 | GSE160308 | GEO
Project description:Diabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Here we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 80 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP−PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. Our findings offer an unprecedented insight into the development of DR and provide potential avenues for future therapeutic intervention.
2021-04-19 | GSE160306 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-04-19 | GSE160310 | GEO
Project description:The development of diabetic retinopathy is well characterized on a histological level. Early vascular alterations involve the loss of pericytes. Earlier mechanisms leading to the phenotype of diabetic retinopathy, which involves the complete neurovascular unit, are not yet fully understood. The gene expression data presented here is derived from microarrays and gives further insights into early genetic regulation in incipient diabetic retinopathy.
2019-01-17 | GSE111465 | GEO
Project description:The goal of the study was to identify genes whose aberrant expression can contribute to diabetic retinopathy. We determined differential response in gene expression to high glucose in lymphoblastoid cell lines derived from matched type 1 diabetic individuals with and without retinopathy. Those genes exhibiting the largest difference in glucose response between diabetic subjects with and without retinopathy were assessed for association to diabetic retinopathy utilizing genotype data from a meta-genome-wide association study. All genetic variants associated with gene expression (expression QTLs; eQTLs) of the glucose response genes were tested for association with diabetic retinopathy. We detected an enrichment of the glucose response gene eQTLs among small association p-values for diabetic retinopathy. Among these, we identified FLCN as a susceptibility gene for diabetic retinopathy. Expression of FLCN in response to glucose is greater in individuals with diabetic retinopathy compared to diabetic individuals without retinopathy. Three large, independent cohorts of diabetic individuals revealed an enhanced association of FLCN eQTL to diabetic retinopathy. Mendelian randomization confirmed a direct positive effect of increased FLCN expression on retinopathy in diabetic individuals. Together, our studies integrating genetic association and gene expression implicate FLCN as a disease gene in diabetic retinopathy.
2020-03-10 | GSE146615 | GEO
Project description:To compare the circRNA expression profile of diabetic retinopathy with that of diabetes mellitus and controls, peripheral blood mononuclear cell samples were obtained and extracted from healthy controls and diabetes mellitus patients (with or without diabetic retinopathy). CircRNA Capital Bio Technology Human CircRNA Array v2 was performed to detect circRNA expression profiles. To further check differentiate circRNA, qRT_PCR assay was performed to detect the level of 5 candidates.
2022-01-21 | GSE193974 | GEO
Project description:Diabetic nephropathy and diabetic retinopathy are related. We used scRNA-seq and RNA-seq to analyze the cellular linkage between them.
2023-08-15 | GSE204880 | GEO
Project description:Background: Proliferative diabetic retinopathy (PDR) is hallmarked by the formation of retinal neovascularization (RNV) membranes, which can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease. The aim of this study was to characterize the molecular and cellular features of RNV in order to unravel potential novel drug treatments for PDR. Methods: A total of 42 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Since macrophages were found to be abundant in RNV tissue, vitreal macrophages, also known as hyalocytes, were isolated from the vitreous of patients with PDR by flow cytometry, cultivated and characterized by immunhistochemistry. A bioinformatical drug repurposing approach was applied, in order to identify novel drug options for end-stage diabetic retinopathy disease. Results: The in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential drug option for future treatment of PDR. Conclusion: This study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and suggests their modulation as a novel possible clinical approach.
2021-10-31 | GSE179568 | GEO