Molecular and functional characterization of circulating extracellular vesicles from diabetic patients with and without retinopathy and healthy subjects

Mazzeo, Aurora; Beltramo, Elena; Lopatina, Tatiana; Gai, Chiara; Trento, Marina; Porta, Massimo

doi:10.1016/j.exer.2018.07.003

Cited by 70 publications

(67 citation statements)

References 47 publications

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“…19 The finding of PDR-specific miRNAs in our study was consistent with other studies [26][27][28] (as shown in Table 3). Recently, miR-150-5p was found to be strongly downregulated in the extracellular vesicles of blood from DR subjects using miRNA array detection 13 and suppression of the pathological neovascularization in mice using oxygeninduced proliferative retinopathy. 29 The possible pathway underlined miR-150-5p may involve decreasing endothelial cell proliferation, migration and tubular formation, as well as suppressing the expression of angiogenic regulators, including CXCR4, DLL4 and FZD4 in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Due to their stability in biofluids such as blood, urine, and aqueous humour (AH), as well as their cell‐type and tissue specificity, miRNAs are potential biomarkers for the detection of DR . A few studies have detected miRNAs in the blood or vitreous humour of DR patients using microarray or polymerase chain reaction (PCR), and suggested that miRNA may be involved in DR and that some miRNAs may be biomarkers for DR . However, miRNA arrays or PCR have only been able to detect some of the mature miRNAs in the known miRbase database .…”

Section: Introductionmentioning

confidence: 99%

“…miRNAs constitute a large family of small (19)(20)(21)(22) nucleotides long), non-coding RNAs that act as post-transcriptional regulators of gene expression. 6 Due to their stability in biofluids such as blood, urine, and aqueous humour (AH), 7 as well as their cell-type and tissue specificity, miRNAs are potential biomarkers for the detection of DR. 4 A few studies have detected miRNAs in the blood or vitreous humour of DR patients using microarray or polymerase chain reaction (PCR), and suggested that miRNA may be involved in DR and that some miRNAs may be biomarkers for DR. [8][9][10][11][12][13] However, miRNA arrays or PCR have only been able to detect some of the mature miRNAs in the known miRbase database. 14,15 No studies have fully detected the entire miRNA profile in AH of DR. Next-generation sequencing (NGS), which not only detects all mature miRNAs, but also predicts novel miRNAs, and have been used to detect the miRNA in AH sample.…”

Section: Introductionmentioning

confidence: 99%

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Landscape of microRNA in the aqueous humour of proliferative diabetic retinopathy as assessed by next‐generation sequencing

Chen

Yuan

Liu

et al. 2019

Clinical Exper Ophthalmology

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Background The microRNAs (miRNA) have been found to play an important role in the pathogenesis of diabetic retinopathy. We try to explore the miRNA and piwi‐interacting RNA (piRNA) profile in the aqueous humour of proliferative diabetic retinopathy (PDR) using next‐generation sequencing (NGS). Methods Aqueous humour samples were collected from nine PDR eyes and nine cataract control eyes, and NGS was performed. Quantitative polymerase chain reaction (qPCR) was used to validate the sequencing results. An oxygen‐induced retinopathy (OIR) model was used to validate the angiogenesis related miRNA. Results In total, 484 miRNAs were differently expressed between the PDR eyes and cataract control eyes, including 210 mature miRNAs and 274 novel miRNAs. Furthermore, eight miRNAs and 30 piRNAs were identified as the most differently expressed between the two groups (P > .85). This differential expression of miRNA was predicted to regulate Rho protein signal transduction, neurotransmitter uptake and histone lysine methylation. Relative expression patterns of miR‐184, ‐150‐5p and ‐93‐5p were confirmed by qPCR. A reduced expression of miR‐93‐5p was confirmed in the OIR model. Conclusions This study comprehensively demonstrated the miRNA and piRNA expression profile of the aqueous humour of PDR eyes, which may serve as a potential biomarker and involved in the pathogenesis of PDR.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Landscape of microRNA in the aqueous humour of proliferative diabetic retinopathy as assessed by next‐generation sequencing

Chen

Yuan

Liu

et al. 2019

Clinical Exper Ophthalmology

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“…miR-221, an anti-angiogenic miRNA, is significantly altered in DM and is involved in the DM physiopathology and macrovascular complications associated with T2DM [113][114][115][116]. In addition, other circulating miRNAs including miR-126 [105][106][107], miR-150 [109], miR-155 [110], and miR-200b [111] are also dysregulated in DR patients, as well as in pre-clinical animal models of DR [143][144][145][146][147][148][149][150][151][152]. These findings indicate the complex regulation of miRNAs in DR and the potential of miRNAs as biomarkers and/or therapeutic targets for treating DR.…”

Section: Mirnas In Drmentioning

confidence: 99%

MicroRNAs in Vascular Eye Diseases

Liu

Huang

Britton

et al. 2020

IJMS

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Since the discovery of the first microRNA (miRNA) decades ago, studies of miRNA biology have expanded in many biomedical research fields, including eye research. The critical roles of miRNAs in normal development and diseases have made miRNAs useful biomarkers or molecular targets for potential therapeutics. In the eye, ocular neovascularization (NV) is a leading cause of blindness in multiple vascular eye diseases. Current anti-angiogenic therapies, such as anti-vascular endothelial growth factor (VEGF) treatment, have their limitations, indicating the need for investigating new targets. Recent studies established the roles of various miRNAs in the regulation of pathological ocular NV, suggesting miRNAs as both biomarkers and therapeutic targets in vascular eye diseases. This review summarizes the biogenesis of miRNAs, and their functions in the normal development and diseases of the eye, with a focus on clinical and experimental retinopathies in both human and animal models. Discovery of novel targets involving miRNAs in vascular eye diseases will provide insights for developing new treatments to counter ocular NV.

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“…Recent studies have detected miRNAs in the blood or vitreous humor of DR patients, suggesting that miRNA may be involved in DR and that some miRNAs may be biomarkers for DR [22][23][24][25][26], but many of them focused on miRNAs expressed in cells or animal models, so the global miRNA pattern in the sera of plasma samples of DR patients has not been determined.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of circulating miR-320a and target gene prediction in patients with diabetic retinopathy

et al. 2020

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Objective: To evaluate the expression of a set of miRNAs to identify differentially expressed miRNAs that might be considered reliable biomarkers on Diabetic Retinopathy (DR) blood samples. were analyzed in 60 healthy controls, 48 Diabetes Melitus (DM) without DR patients and 62 DR patients by qRT-PCR. MiR-320a was shown to be downregulated in the plasma of DR patients compared with DM patients without DR and healthy subjects. Target genes were predicted using miRWalk3.0, miR targeting data and target gene interaction data were imported to Cytoscape to visualize and merge networks and top ranked predicted genes were run through Ontology Genes to perform enrichment analysis on gene sets and classification system to identify biological processes and reactome pathways associated with DR. Highly scored target genes of miR-320a were categorized for various biological processes, including negative regulation of cell aging, negative regulation of cellular protein metabolic process and regulation of cellular response to stress that are critical to the development of DR. Our findings suggest that MiR-320a may have a role in the pathogenesis of DR and may represent novel biomarkers for this disease. Results: Expression levels of

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Molecular and functional characterization of circulating extracellular vesicles from diabetic patients with and without retinopathy and healthy subjects

Cited by 70 publications

References 47 publications

Landscape of microRNA in the aqueous humour of proliferative diabetic retinopathy as assessed by next‐generation sequencing

Landscape of microRNA in the aqueous humour of proliferative diabetic retinopathy as assessed by next‐generation sequencing

MicroRNAs in Vascular Eye Diseases

Downregulation of circulating miR-320a and target gene prediction in patients with diabetic retinopathy

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