Association between lncRNAs in plasma exosomes and diabetic retinopathy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE212594 | GEO | 2022/09/06
REPOSITORIES: GEO
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Project description:Diabetic retinopathy (DR) is a common microvascular complication that may cause severe visual impairment and blindness in patients with type 2 diabetes mellitus (T2DM). Early detection of DR will provide opportunities for more treatment options and better control of disease progression. Effective biomarkers, which are not currently available, may improve clinical outcomes through precise diagnosis and prognosis. We sought to develop a non-invasive diagnostic approach for diabetic retinopathy among type 2 diabetes mellitus based on 5-hydroxymethylcytosines (5hmC), an emerging epigenetic marker, in circulating cell-free DNA (cfDNA)
2021-11-20 | GSE140842 | GEO
Project description:To investigate the possibilities of circulating exosomal miRNAs in the early screening and prevention of diabetic retinopathy(DR), and to explore how the exosomal miRNAs functioning in DR. We then performed gene expression profiling analysis using data obtained from small RNA-seq of 3 diabetes mellitus(DM) patients and 3 DR patients.
2023-07-12 | GSE221535 | GEO
Project description:To understand the association between systemic factors and the diabetic retinopathy, blood samples were collected in 50 healthy controls, 74 diabetic patients without diabetic retinopathy (DM group), and 69 diabetic retinopathy (DR Group). T1DM and T2DM in this study was based on the diagnostic criteria for diabetes proposed by the WHO in 1999. The diagnosis of DR was based on the international clinical classification of DR proposed at the 2002 International Ophthalmology Conference. We then performed gene expression profiling analysis using data obtained from RNA-seq of three patient groups.
2023-05-26 | GSE221521 | GEO
Project description:Diabetic retinopathy (DR) is one of the common chronic complications of diabetes. Circular RNA (circRNA) plays a vital role in the pathological process of diabetic retinopathy (DR), this study aims to explore the differences in circRNA expression profiles and functions between DR and non-DR patients.Serum from diabetes mellitus (DM) patients with DR (n=5) and without DR (n=5) were extracted for circRNA microarray analysis using Arraystar Human circRNA expression profile (v2.0). Another 5 DR and 5 non-DR patients were included for quantitative reverse transcription polymerase chain reaction (RT-qPCR) validation. Enriched signaling pathways were analyzed by GO and KEGG analysis. circRNA–miRNA networks were constructed by bioinformatics analysis.
2024-09-02 | GSE276127 | GEO
Project description:PURPOSE: To investigate the circulatory microRNA (miRNA) profiles of aqueous, vitreous, and plasma in order to identify biomarkers in aqueous humor or plasma that are reflecting changes in vitreous of patients with diabetes. METHODS: Aqueous, vitreous and plasma samples were collected from a total of 27 patients - 11 controls (macular pucker or macular hole patients) and 16 patients with diabetes mellitus (DM) undergoing vitreoretinal surgery: DM-Type I with proliferative diabetic retinopathy (PDR) (DMI-PDR), DM Type II with PDR (DMII-PDR) and DM Type II with nonproliferative DR (DMII-NPDR). MiRNAs were isolated using Qiagen microRNeasy kit, quantified on BioAnalyzer, labeled with FlashTag kit, and profiled on Affymetrix GeneChip miRNA 3.0 microarrays. Data analysis was done using Expression Console (EC), Transcriptome Analysis Console (TAC), and Ingenuity Pathway Analysis (IPA) software. RESULTS: Our comparison of circulatory miRNA population of aqueous and vitreous humor and plasma showed that out of total of 847 human miRNA probes on the Affymetrix GeneChip miRNA 3.0 we found common miRNAs for both aqueous and vitreous samples, as well as larger number of unique miRNA, dependent on the DM type and presence of retinopathy. Most of the dysregulated miRNAs in aqueous and vitreous of DM patients were upregulated, while in plasma, most of the DM-specific miRNAs were downregulated. Dysregulation of miRNAs in aqueous generally do not appear to be a good representative of the miRNA abundance in vitreous, or plasma, although we did identify a few candidates for common biomarkers: let-7b, miR-320b, miR-762 and miR-4488. Additionally, each of the DR subtypes showed a set of miRNA that is uniquely dysregulated in each fluid, for example in aqueous samples for DMII-NPDR it was miR-455-3p, for DMII-PDR was miR-296, and for DMI-PDR it was miR-3202. Pathway analysis identified TGF-beta and VEGF pathways as the common targets for miRNAs dysregulated in DR aqueous and vitreous. CONCLUSIONS: The comparative profiling of circulatory miRNAs in aqueous, vitreous, and plasma showed that a small number of circulatory miRNAs displayed differential presence in controls vs. diabetic retinopathy. A pattern is emerging of sets of miRNA that are common or uniquely dysregulated in the blood plasma or ocular fluids of DR subtypes, offering promise for the use of ocular fluids and plasma for identifying diagnostic and therapeutic targets.
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Project description:Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and dyslipidemia leads to non-proliferative diabetic retinopathy (NPDR). NPDR is associated with blood-retinal barrier disruption, plasma exudates, microvascular degeneration, elevated inflammatory cytokine levels and monocyte (Mo) infiltration. Whether and how the diabetes-associated changes in plasma lipid and carbohydrate levels modify Mo differentiation. Here, we show that mononuclear phagocytes (MPs) in areas of vascular leakage in DR donor retinas express PLIN2, a marker of intracellular lipid load. Strong upregulation of PLIN2 was also observed when healthy donor Mos were treated with plasma from T2DM patients or with palmitate concentrations typical of T2DM plasma, but not under high glucose conditions. PLIN2 expression correlated with the expression of other key genes involved in lipid metabolism (ACADVL, PDK4) and the DR biomarkers ANGPTL4 and CXCL8. Mechanistically, we show that lipid-exposed MPs induce capillary degeneration in ex vivo explants, which was inhibited by pharmaceutical inhibition of PPARγ signaling. Our study provides a novel mechanism linking dyslipidemia-induced MP polarization to the increased inflammatory cytokine levels and microvascular degeneration that characterize NPDR. This study provides comprehensive insights into the glycemia-independent activation of Mos in T2DM and identifies MP PPARγ as a target to inhibit lipid-activated MPs in DR
2023-08-31 | GSE239512 | GEO
Project description:Identification of tear fluid biomarkers may offer a non-invasive strategy for detecting diabetic patients with increased risk of developing diabetic retinopathy (DR) or increased disease progression, thus helping both improving diagnostic accuracy and understanding the pathophysiology of the disease. The goal of this study was to characterize the proteomic profile of human tear fluid and examine changes in proteins expression in different stages of diabetic retinopathy.
2022-05-31 | PXD033101 | Pride
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:Circulating immune cells play a role in the pathophysiology of diabetic retinopathy (DR). Our study focused on examining the exact role of circulating immune cells in the development of DR. Single-cell RNA sequencing (scRNA-seq) techniques revealed unique differentially-expressed genes and pathways in circulating immune cells among non-diabetic retinopathy (NDR) patients and DR patients. These findings highlight the notable alterations in the immunophenotypes of circulating immune cells in patients with type 1 DR.
2024-02-14 | GSE248284 | GEO
Project description:Diabetic retinopathy (DR) is a major complication of diabetes mellitus causing significant vision loss. Despite the success of anti-VEGF therapy as an effective therapy, many DR patients do not respond well to the treatment, emphasizing the involvement of other molecular players. To unveil these, we performed deep vitreous proteome profiling of patients with proliferative DR and extracted aberrated protein networks. This revealed impairment in ectodomain shedding of several transmembrane proteins playing critical roles in neurodegeneration and angiogenesis, that pointed to defects in their regulating sheddases, particularly ADAM10, which emerged as the predominant sheddase. We confirmed that ADAM10 protease activity was reduced in ocular disease models and established that activation of ADAM10 can suppress endothelial cell activation and angiogenesis. Furthermore, we identified impaired ADAM10-AXL axis as a retinal angiogenic driver. Taken together, we demonstrate restoration of aberrant ectodomain shedding as an effective strategy for treating DR and propose ADAM10 as an attractive novel target.
2022-10-14 | PXD036033 | Pride