Molecular and functional characterization of circulating extracellular vesicles from diabetic patients with and without retinopathy and healthy subjects. (November 2018)

• Record Type: Journal Article
• Authors: Mazzeo, Aurora; Beltramo, Elena; Lopatina, Tatiana; Gai, Chiara; Trento, Marina; Porta, Massimo
• Is Part Of: Experimental eye research. Volume 176(2018)
• Page Start: 69
• Page End: 77
• Publication Date: 2018-11
• Subjects: Diabetes -- Diabetic retinopathy -- Extracellular vesicles -- Angiogenesis -- miR-150-5p -- miR-21-3p -- miR-30b-5p -- Pericytes; CTR group of healthy controls -- DR group of diabetic patients with retinopathy -- EC endothelial cell -- ECM extracellular matrix -- EV extracellular vesicles -- HMEC human microvascular endothelial cells -- HRP human retinal pericytes -- HIF-1α hypoxia-inducible factor 1 α -- KEGG Kyoto Encyclopedia of Genes and Genomes -- miRNA miR, microRNA -- MSC mesenchymal stem cells -- noDR group of diabetic patients without retinopathy -- PS phosphatidyl-serine -- VEGF vascular endothelial growth factor -- VEGFR1/2 vascular endothelial growth factor receptor 1/2; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2018.07.003
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Diabetic retinopathy is a sight-threatening complication of diabetes, characterized by loss of retinal pericytes and abnormal angiogenesis. We previously demonstrated that extracellular vesicles (EVs) derived from mesenchymal stem cells cultured in diabetic-like conditions are able to enter the pericytes, causing their detachment and migration, and stimulating angiogenesis in vitro . The purpose of this work was the molecular and functional characterization of EVs derived from diabetic subjects with or without diabetic retinopathy, compared with healthy controls. Characterization of EVs extracted from serum/plasma of diabetic patients with or without retinopathy, and healthy controls, was performed by FACS and microarray analysis of microRNA (miRNA) content. Relevant miRNA expression was validated through qRT-PCR. EV influence on pericyte detachment, angiogenesis and permeability of the blood-retinal barrier was also investigated. Diabetic subjects had a 2.5 fold higher EV concentration than controls, while expression of surface molecules was unchanged. Microarray analysis revealed 11 differentially expressed miRNAs. Three of them (miR-150-5p, miR-21-3p and miR-30b-5p) were confirmed by qRT-PCR. Plasma EVs from subjects with diabetic retinopathy induced pericyte detachment and pericyte/endothelial cell migration, increased the permeability of pericyte/endothelial cell bilayers and the formation of vessel-like structures, when compared with EVs from controls. In conclusion, circulating EVs show differences between diabetic patients and healthy subjects. EVs extracted from plasma of diabetic retinopathy patients are able to induce features of retinopathy in in vitro models of retinal microvasculature. Our data suggest a role for miR-150-5p, miR-21-3p and miR-30b-5p as potential biomarkers of the onset of diabetic retinopathy. Highlights: Circulating extracellular vesicles are different in diabetic and healthy subjects. Vesicles from diabetic retinopathy patients induce features of retinopathy in vitro . MiRNAs shuttled by extracellular vesicles are involved. miR-150-5p, miR-21-3p, miR-30b-5p are potential biomarkers of diabetic retinopathy.