Dataset Information

MicroRNA Expression in the Aqueous Humor of Patients with Diabetic Macular Edema.

ABSTRACT: We identified and compared secreted microRNA (miRNA) expression in aqueous humor (AH) and plasma samples among patients with: type 2 diabetes mellitus (T2D) complicated by non-proliferative diabetic retinopathy (DR) associated with diabetic macular edema (DME) (DME group: 12 patients); T2D patients without DR (D group: 8 patients); and non-diabetic patients (CTR group: 10 patients). Individual patient AH samples from five subjects in each group were profiled on TaqMan Low Density MicroRNA Array Cards. Differentially expressed miRNAs identified from profiling were then validated in single assay for all subjects. The miRNAs validated in AH were then evaluated in single assay in plasma. Gene Ontology (GO) analysis was conducted. From AH profiling, 119 mature miRNAs were detected: 86 in the DME group, 113 in the D group and 107 in the CTR group. miRNA underexpression in the DME group was confirmed in single assay for let-7c-5p, miR-200b-3p, miR-199a-3p and miR-365-3p. Of these four, miR-199a-3p and miR-365-3p were downregulated also in the plasma of the DME group. GO highlighted 54 validated target genes of miR-199a-3p, miR-200b-3p and miR-365-3p potentially implied in DME pathogenesis. Although more studies are needed, miR-200b-3p, let-7c-5p, miR-365-3p and miR-199a-3p represent interesting molecules in the study of DME pathogenesis.

SUBMITTER: Grieco GE

PROVIDER: S-EPMC7582592 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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MicroRNA Expression in the Aqueous Humor of Patients with Diabetic Macular Edema.

Grieco Giuseppina Emanuela GE Sebastiani Guido G Eandi Chiara Maria CM Neri Giovanni G Nigi Laura L Brusco Noemi N D'Aurizio Romina R Posarelli Matteo M Bacci Tommaso T Benedetto Elena De E Fruschelli Mario M Orlandini Maurizio M Galvagni Federico F Dotta Francesco F Tosi Gian Marco GM

International journal of molecular sciences 20201003 19

We identified and compared secreted microRNA (miRNA) expression in aqueous humor (AH) and plasma samples among patients with: type 2 diabetes mellitus (T2D) complicated by non-proliferative diabetic retinopathy (DR) associated with diabetic macular edema (DME) (DME group: 12 patients); T2D patients without DR (D group: 8 patients); and non-diabetic patients (CTR group: 10 patients). Individual patient AH samples from five subjects in each group were profiled on TaqMan Low Density MicroRNA Array ...[more]

PMID: 33023063

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Project description:Variability in response to anti-vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help anticipate responses to anti-VEGF therapy.To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response.In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 μm or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up.Participants received monthly injections of ranibizumab, 0.5 mg, for 3 months. Aqueous fluid for cytokine analysis was obtained at baseline and repeated at the 2-month visit. Multiplex immunoassay was carried out in duplicate for VEGF, placental growth factor, transforming growth factor beta 2, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), IL-8, IL-10, vascular intercellular adhesion molecule, and monocyte chemoattractant protein 1.Baseline and 2-month change in aqueous cytokine levels, 3-month change in SD-OCT central subfield thickness and macular volume (MV), and the statistical association between baseline aqueous cytokine levels and these measures of anatomic response to ranibizumab in center-involving DME.Among the 48 participants, the mean (SD) age was 61.9 (7.1) years and 36 participants (75.0%) were men. The following cytokines were lower at month 2 vs baseline: ICAM-1 (median change, -190.88; interquartile range [IQR], -634.20 to -26.54; P < .001), VEGF (median change, -639.45; IQR, -1040.61 to -502.61; P < .001), placental growth factor (median change, -1.31; IQR, -5.99 to -0.01; P < .001), IL-6 (median change, -38.61; IQR, -166.72 to -2.80; P < .001), and monocyte chemoattractant protein 1 (median change, -90.13; IQR, -382.74 to 109.47; P = .01). When controlling for age, foveal avascular zone size, and severity of retinopathy, multiple linear regression determined that increasing baseline aqueous ICAM-1 was associated with a favorable anatomic response, in terms of reduced SD-OCT MV at 3 months (every additional 100 pg/mL of baseline ICAM-1 was associated with a reduction of 0.0379 mm3; P = .01). Conversely, increasing baseline aqueous VEGF was associated with a less favorable SD-OCT MV response at 3 months (every additional 100 pg/mL of baseline VEGF was associated with an increase of 0.0731 mm3; P = .02) and was associated with lower odds of being a central subfield thickness responder (odds ratio, 0.868; 95% CI, 0.755-0.998).Elevated aqueous ICAM-1 and reduced VEGF levels at baseline are associated with a favorable anatomic response to ranibizumab in DME, although there is not always direct correlation between anatomic and visual acuity response.

Project description:Macular edema (ME) is the main cause of visual impairment in patients with retinal vein occlusion (RVO). The degree of ME affects the prognosis of RVO patients, while it lacks objective laboratory biomarkers. We aimed to compare aqueous humor samples from 28 patients with retinal vein occlusion macular edema (RVO-ME) to 27 age- and sex-matched controls by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry, so as to identify the key biomarkers and to increase the understanding of the mechanism of RVO-ME at the molecular level. Through univariate and multivariate statistical analyses, we identified 60 metabolites between RVO-ME patients and controls and 40 differential metabolites in mild RVO-ME [300 μm ≤ central retinal thickness (CRT) < 400 μm] patients compared with severe RVO-ME (CRT ≥ 400 μm). Pathway enrichment analysis showed that valine, leucine, and isoleucine biosynthesis; ascorbate and aldarate metabolism; and pantothenate and coenzyme A biosynthesis were significantly altered in RVO-ME in comparison with controls. Compared with mild RVO-ME, degradation and biosynthesis of valine, leucine, and isoleucine; histidine metabolism; beta-alanine metabolism; and pantothenate and coenzyme A biosynthesis were significantly changed in severe RVO-ME. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that adenosine, threonic acid, pyruvic acid, and pyro-L-glutaminyl-l-glutamine could differentiate RVO-ME from controls with an area under the curve (AUC) of >0.813. Urocanic acid, diethanolamine, 8-butanoylneosolaniol, niacinamide, paraldehyde, phytosphingosine, 4-aminobutyraldehyde, dihydrolipoate, and 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide had an AUC of >0.848 for distinguishing mild RVO-ME from severe RVO-ME. Our study expanded the understanding of metabolomic changes in RVO-ME, which could help us to have a good understanding of the pathogenesis of RVO-ME.

Project description:Diabetic macular edema (DME) is the main cause of visual impairment in diabetic patients, but its pathogenesis remains unclear. The purpose of the present study was to analyze the expression of microRNA (miR)-155-5p in patients with DME and its regulatory mechanism. A total of 72 patients diagnosed with DME and 17 with idiopathic macular hole (MH) were recruited. Among samples from patients with DME, 45 were DME and 27 were refractory DME, whereas patients with idiopathic MH served as the control group. Optical coherence tomography and fundus photograph analysis revealed that part of the retina in the fundus of patients with DME was thickened, with macular edema occurring simultaneously. In refractory patients with DME, macular edema was associated with bleeding and a dark cavity between retinal layers. Through reverse transcription-quantitative PCR analysis, miR-155-5p was highly expressed in the aqueous humor (AH) and plasma of patients with DME compared with that in patients with MH, and this was even higher in the refractory DME group. Upon analyzing patient clinical data, the difference in miR-155-5p expression in the AH and plasma was positively associated with disease course, body mass index, fasting blood-glucose, glycated hemoglobin, proteinuria and glycosuria. The expression of miR-155-5p was not significantly different based on hemoglobin, intraocular pressure and sex. The aforementioned results indicate that miR-155-5p might promote the development of DME. To further study the molecular mechanism, human retinal microvascular endothelial cells (HRMECs) were cultured and treated with high glucose in vitro. The results showed that miR-155-5p expression was significantly upregulated in HRMECs induced by high glucose. After inhibiting the expression of miR-155-5p, cell proliferation, angiogenesis and VEGF protein levels were significantly downregulated, whereas miR-155-5p mimics had the opposite effect. In summary, miR-155-5p is closely associated with DME and is a potential target for refractory DME treatment.

Project description:PurposeTo investigate the aqueous levels of angiogenic factors in nonproliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME) and to ascertain their association with optical coherence tomography angiography (OCTA) metrics.MethodsThis study enrolled 21 NPDR eyes with DME (NPDR/DME+), 17 NPDR eyes without DME (NPDR/DME-), and 16 diabetic eyes without retinopathy (DWR). Luminex bead-based multiplex array was used to measure the levels of 25 cytokines. OCTA system with a scan area of 3 × 3 mm was used to measure retinal thickness (RT), retinal volume (RV), superficial vessel density (SVD), deep vessel density (DVD), foveal avascular zone (FAZ) area, perimeter and acircularity index.ResultsThe levels of ANGPTL4 were significantly different among the three groups (P < 0.05), in which NPDR/DME+ group had the highest level and NPDR/DME- group had a higher level than the DWR group (all, P < 0.0167). OCTA examination showed that, compared with DWR and NPDR/DME- group, RT and RV increased and the whole/parafoveal DVD decreased in NPDR/DME+ group (all, P < 0.05). Meanwhile, NPDR/DME- group had lower parafoveal DVD than the DWR group (P < 0.05). Correlation analysis showed that the levels of ANGPTL4 were positively correlated with foveal/parafoveal RT and RV and negatively correlated with whole/parafoveal DVD in NPDR patients (all, P < 0.05). As the influencing factor of RT, RV, and DVD, every additional 103 pg/ml of ANGPTL4 was associated with an increase in foveal and parafoveal RT of 4.299 μm and 3.598 μm, respectively. Every additional 106 pg/ml of ANGPTL4 was associated with an increase in foveal and parafoveal RV of 3.371 mm3 and 17.705 mm3, respectively. Every additional 104 pg/ml of ANGPTL4 was associated with a decrease in whole and parafoveal DVD of 1.705% and 1.799%, respectively.ConclusionsThe level of ANGPTL4 in aqueous humor of NPDR patients with DME was significantly increased and ANGPTL4 might predict RT, RV, and parafoveal DVD of DME in NPDR patients.

Dataset Information

MicroRNA Expression in the Aqueous Humor of Patients with Diabetic Macular Edema.

Publications

MicroRNA Expression in the Aqueous Humor of Patients with Diabetic Macular Edema.

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