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

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.

journal_name

Exp Eye Res

authors

Mazzeo A,Beltramo E,Lopatina T,Gai C,Trento M,Porta M

doi

10.1016/j.exer.2018.07.003

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

69-77

eissn

0014-4835

issn

1096-0007

pii

S0014-4835(18)30108-8

journal_volume

176

pub_type

杂志文章
  • Functional and anatomical remodeling in human retinal detachment.

    abstract::Rhegmatogenous retinal detachment is by far the most common indication for retinal surgery and a major cause of severe vision loss. Increased levels of glutamate found in the vitreous of human patients and persistent remodeling, even after reattachment, suggest substantial neurochemical, functional and anatomical chan...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2012.02.009

    authors: de Souza CF,Kalloniatis M,Polkinghorne PJ,McGhee CN,Acosta ML

    更新日期:2012-04-01 00:00:00

  • Osmoregulatory alterations in myo-inositol uptake by bovine lens epithelial cells. III. Effects of cycloheximide and colchicine on Na(+)-myo-inositol cotransporter activity under hypertonic conditions, inhibition of a plasma membrane osmotic stress protei

    abstract::Cultured bovine lens epithelial cells adapt to hypertonic sodium stress via an increase in Na(+)-myo-inositol cotransporter activity and accumulate myo-inositol. At least 12 hr of hypertonic exposure was necessary to enhance myo-inositol accumulation; and thereafter, uptake activity continued to increase throughout th...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1006/exer.1994.1083

    authors: Cammarata PR,Chen HQ,Zhou C,Reeves R

    更新日期:1994-07-01 00:00:00

  • Distribution of cathepsin D in human eyes with or without age-related maculopathy.

    abstract::Cathepsin D is a ubiquitous enzyme which plays an important role in the catabolism of proteins. Enzymatic studies showed that cathepsin D is the most important lysosomal enzyme in the proteolysis of opsin. The importance of cathepsin D in the lysosomal digestion of phagocytosed photoreceptor outer segments by the reti...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1006/exer.1999.0700

    authors: Rakoczy PE,Sarks SH,Daw N,Constable IJ

    更新日期:1999-10-01 00:00:00

  • Transcriptomics analysis of pericytes from retinas of diabetic animals reveals novel genes and molecular pathways relevant to blood-retinal barrier alterations in diabetic retinopathy.

    abstract::Selective pericyte loss, the histological hallmark of early diabetic retinopathy (DR), enhances the breakdown of the blood-retinal barrier (BRB) in diabetes. However, the role of pericytes on BRB alteration in diabetes and the signaling pathways involved in their effects are currently unknown. To understand the role o...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2020.108043

    authors: Rangasamy S,Monickaraj F,Legendre C,Cabrera AP,Llaci L,Bilagody C,McGuire P,Das A

    更新日期:2020-06-01 00:00:00

  • Intravitreal administration of endothelin type A receptor or endothelin type B receptor antagonists attenuates hypertensive and diabetic retinopathy in rats.

    abstract::Hypertension is an independent risk factor for diabetic retinopathy, yet anti-hypertensive medications such as blockade of angiotensin II do not completely protect against vision-threatening vascular disease. We hypothesized that the potent vasoactive factor, endothelin (ET), is up-regulated in diabetic retinopathy an...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2018.06.025

    authors: Alrashdi SF,Deliyanti D,Wilkinson-Berka JL

    更新日期:2018-11-01 00:00:00

  • Non-tryptophan fluorescence and high molecular weight protein formation in lens crystallins of rats with chronic galactosemia: prevention by the aldose reductase inhibitor sorbinil.

    abstract::Crystallin-bound non-tryptophan fluorescence and protein cross-linking were studied in chronic galactosemia. Fluorescence (excitation/emission--370/440 nm) was significantly higher in galactosemic rats compared to controls (P less than 0.001). Accumulation of fluorescence was significantly reduced both in water solubl...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/0014-4835(90)90153-l

    authors: Nagaraj RH,Monnier VM

    更新日期:1990-10-01 00:00:00

  • Functional analysis of miR-21-3p, miR-30b-5p and miR-150-5p shuttled by extracellular vesicles from diabetic subjects reveals their association with diabetic retinopathy.

    abstract::Microvascular dysfunctions due to altered interactions between endothelial cells (ECs) and pericytes are key-events in the pathogenesis of diabetic retinopathy. Extracellular vesicles (EVs) derived from mesenchymal stem cells cultured in diabetic-like conditions enter pericytes, cause their detachment and migration, a...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2019.04.015

    authors: Mazzeo A,Lopatina T,Gai C,Trento M,Porta M,Beltramo E

    更新日期:2019-07-01 00:00:00

  • Optical treatment strategies to slow myopia progression: effects of the visual extent of the optical treatment zone.

    abstract::In order to develop effective optical treatment strategies for myopia, it is important to understand how visual experience influences refractive development. Beginning with the discovery of the phenomenon of form deprivation myopia, research involving many animal species has demonstrated that refractive development is...

    journal_title:Experimental eye research

    pub_type: 杂志文章,评审

    doi:10.1016/j.exer.2012.11.019

    authors: Smith EL 3rd

    更新日期:2013-09-01 00:00:00

  • Loss of photoreceptor potential from retinal progenitor cell cultures, despite improvements in survival.

    abstract::Retinal degeneration (RD) results from photoreceptor apoptosis. Cell transplantation, one potential therapeutic approach, requires expandable stem cells that can form mature photoreceptors when differentiated. Freshly dissociated primary retinal cells from postnatal day 2-6 (PN2-6) mouse retina can give rise, post-tra...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2010.07.003

    authors: Mansergh FC,Vawda R,Millington-Ward S,Kenna PF,Haas J,Gallagher C,Wilson JH,Humphries P,Ader M,Farrar GJ

    更新日期:2010-10-01 00:00:00

  • Natural, high-mannose glycoproteins inhibit ROS binding and ingestion by RPE cell cultures.

    abstract::Previous studies have suggested that a mannose receptor mediates the phagocytic uptake of effete rod outer segments by retinal pigment epithelial cells. In the present study, the effect of adding a soluble ligand for the mannose receptor, horseradish peroxidase, was examined. Cultured retinal pigment epithelial cells ...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/s0014-4835(05)80144-7

    authors: Lutz DA,Guo Y,McLaughlin BJ

    更新日期:1995-10-01 00:00:00

  • Effects of substance P on inositol triphosphate accumulation, on contractile responses and on arachidonic acid release and prostaglandin biosynthesis in rabbit iris sphincter muscle.

    abstract::Addition of substance P (10(-7) to 10(-6) M) to rabbit iris sphincter muscle induced: (a) a rapid phosphodiesteratic breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) into 1,2-diacylglycerol (DG), measured as phosphatidic acid, and inositol triphosphate (IP3), measured by anion-exchange chromatography; (b) a r...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/s0014-4835(86)80089-6

    authors: Yousufzai SY,Akhtar RA,Abdel-Latif AA

    更新日期:1986-08-01 00:00:00

  • Aqueous humor tyrosinase activity is indicative of iris melanocyte toxicity.

    abstract::Antibiotics such as fluoroquinolones (FQLs) are commonly used to treat ocular infections but are also known to cause dermal melanocyte toxicity. The release of dispersed pigments from the iris into the aqueous humor has been considered a possible ocular side effect of the systemic administration of FQLs such as Moxifl...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2017.07.006

    authors: Mahanty S,Kawali AA,Dakappa SS,Mahendradas P,Kurian M,Kharbanda V,Shetty R,Setty SRG

    更新日期:2017-09-01 00:00:00

  • Hypertonic stress induces alpha B-crystallin expression.

    abstract::Alpha B-crystallin, a major lens protein, was induced in primary cultures of dog lens epithelial cells and glomerular endothelial cells when they were grown under conditions of hypertonic stress. With Western blot analysis using a specific alpha B-crystallin antibody, we observed a significant increase in the concentr...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/0014-4835(92)90058-z

    authors: Dasgupta S,Hohman TC,Carper D

    更新日期:1992-03-01 00:00:00

  • Rat BMSCs initiate retinal endogenous repair through NGF/TrkA signaling.

    abstract::Müller cells can completely repair retinal injury by acting as endogenous stem/progenitor cells in lower-order vertebrates. However, a safe and effective approach to activate progenitor potential of retinal Müller cells in higher-order vertebrates, which rarely re-enter the cell cycle, is a bottleneck problem. In the ...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2015.01.008

    authors: Jian Q,Li Y,Yin ZQ

    更新日期:2015-03-01 00:00:00

  • High-mobility group Box-1 is involved in NMDA-induced retinal injury the in rat retina.

    abstract::High-mobility group Box-1 (HMGB1) is known to be released from injured cells and to induce an inflammatory response. Although HMGB1 was reported to mediate ischemia-reperfusion injury of the brain, its role in glutamate excitotoxicity of the retina remains controversial. Here, the authors demonstrated the evidence tha...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2015.06.003

    authors: Sakamoto K,Mizuta A,Fujimura K,Kurauchi Y,Mori A,Nakahara T,Ishii K

    更新日期:2015-08-01 00:00:00

  • Effects of norepinephrine and 5-hydroxytryptamine on phosphoinositide-PO4 turnover in rabbit cornea.

    abstract::We have investigated: (a) Phospholipid composition and phosphoinositide-PO4 turnover in rabbit cornea tissues; and (b) the effects of adrenergic and serotonergic agonists on breakdown of phosphoinositides in the rabbit cornea. The data obtained from these studies can be summarized as follows: (1) in the cornea phospha...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/s0014-4835(87)80047-7

    authors: Akhtar RA

    更新日期:1987-06-01 00:00:00

  • Distribution of pterygopalatine ganglion efferents to the lacrimal gland in man.

    abstract::To trace the path taken by the putative postganglionic secretomotor fibres to the lacrimal gland the contents of the orbital and pterygopalatine fossa were removed whole, cut coronally into slabs and embedded in resin. Thin sections were cut at varying intervals to reconstruct the pathway taken. One group of rami orbi...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2003.06.001

    authors: Ruskell GL

    更新日期:2004-03-01 00:00:00

  • Injury and nucleotides induce phosphorylation of epidermal growth factor receptor: MMP and HB-EGF dependent pathway.

    abstract::The early events that occur rapidly after injury trigger signal cascades that are essential for proper wound closure of corneal epithelial cells. We hypothesize that injury releases ATP, which stimulates purinergic receptors and elicits the phosphorylation of epidermal growth factor receptor (EGFR) tyrosine residues a...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2007.03.009

    authors: Boucher I,Yang L,Mayo C,Klepeis V,Trinkaus-Randall V

    更新日期:2007-07-01 00:00:00

  • Signal transduction mechanisms involved in ischemic preconditioning in the rat retina in vivo.

    abstract::Ischemic preconditioning (IPC) protects the rat retina against the injury that ordinarily follows severe ischemia. We showed previously that release of adenosine and de novo protein synthesis were required for IPC protection. The mechanisms of IPC were studied in the rat retina by examining the signal transduction med...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1006/exer.2000.0843

    authors: Li B,Yang C,Rosenbaum DM,Roth S

    更新日期:2000-06-01 00:00:00

  • Expression of inwardly rectifying potassium channel subunits in native human retinal pigment epithelium.

    abstract::Previously, we demonstrated that the inwardly rectifying K(+) (Kir) channel subunit Kir7.1 is highly expressed in bovine and human retinal pigment epithelium (RPE). The purpose of this study was to determine whether any of the 14 other members of the Kir gene family are expressed in native human RPE. Conventional reve...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2008.05.010

    authors: Yang D,Zhang X,Hughes BA

    更新日期:2008-09-01 00:00:00

  • Lipid-mediated gene transfer of acidic fibroblast growth factor into human corneal endothelial cells.

    abstract::The aim of this study was to optimize non-viral gene transfer conditions and investigate the effect of fibroblast growth factor-1 (FGF-1) gene transfer on human corneal endothelial cell (HCEC) proliferation. Five non-viral vectors (Lipofectin, DMRIE-C, DAC-30, Effectene, FuGene6) were used to transfect HCEC with plasm...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2004.08.024

    authors: Dannowski H,Bednarz J,Reszka R,Engelmann K,Pleyer U

    更新日期:2005-01-01 00:00:00

  • Studies on ocular inflammation and development of a prostaglandin analogue for glaucoma treatment.

    abstract::This review summarizes the Ernst H. Bárány Prize Lecture given at the meeting of the International Society of Eye Research in Geneva 2002. In the paper the path from the author's early studies on neurogenic inflammation in the eye to the search for a suitable prostaglandin analogue for glaucoma treatment, and the deve...

    journal_title:Experimental eye research

    pub_type: 杂志文章,评审

    doi:10.1016/j.exer.2003.11.016

    authors: Stjernschantz J

    更新日期:2004-04-01 00:00:00

  • Inhibition of vascular endothelial cell growth and trypsin activity by vitreous.

    abstract::Vitreous from bovine, human and chick embryo has been found to contain a trypsin inhibitory activity. Chymotrypsin-inhibitory activity was also identified in bovine and chick embryo vitreous. Following either ultrafiltration or Bio Gel P-10 chromatography, these activities appear in fractions having a molecular weight...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/0014-4835(85)90031-4

    authors: Jacobson B,Dorfman T,Basu PK,Hasany SM

    更新日期:1985-11-01 00:00:00

  • Overexpression of S100A4 protects retinal ganglion cells against retinal ischemia-reperfusion injury in mice.

    abstract:BACKGROUND:Glaucoma is characterized by the neurodegeneration of retinal ganglion cells (RGCs) and the optic nerve. Numerous studies have reported that S100A4 participates in the metastasis of tumor cells and nerve protection. This study was intended to explore the role of S100A4 on RGCs under retinal ischemia-reperfus...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2020.108281

    authors: Yang J,Yang N,Luo J,Cheng G,Zhang X,He T,Xing Y

    更新日期:2020-12-01 00:00:00

  • Endotoxin-induced uveitis in the rat: observations on altered vascular permeability, clinical findings, and histology.

    abstract::A single intraperitoneal dose of endotoxin (lipopolysaccharide or LPS) induces an acute inflammatory response in the uveal tract of rats. This inflammation is characterized by a breakdown of the blood/aqueous barrier within 3 hr after the LPS and the subsequent development of clinical disease and a cellular infiltrate...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/0014-4835(84)90065-4

    authors: Cousins SW,Guss RB,Howes EL Jr,Rosenbaum JT

    更新日期:1984-11-01 00:00:00

  • Early monocular enucleation selectively disrupts neural development of face perception in the occipital face area.

    abstract::Retinoblastoma generally occurs before 5 years of age and often requires enucleation (surgical removal of one eye) of the cancerous eye. We have previously shown using behavioural methods that this disruption in binocular vision during the critical period of visual development results in impaired face perception. In t...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2018.09.013

    authors: Kelly KR,Gallie BL,Steeves JKE

    更新日期:2019-06-01 00:00:00

  • A splice variant of arrestin from human retina.

    abstract::Retinal arrestin is known to participate in the quenching of phototransduction through binding to light-activated and phosphorylated rhodopsin. Recently, a splice variant of retinal arrestin was identified in bovine photoreceptors which could bind unphosphorylated photoactive rhodopsin. In this report, a splice varian...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1006/exer.1996.0069

    authors: Smith WC

    更新日期:1996-06-01 00:00:00

  • Distribution, spherical structure and predicted Mie scattering of multilamellar bodies in human age-related nuclear cataracts.

    abstract:PURPOSE:To characterize multilamellar bodies (MLBs), determine their distribution along the optic axis and predict their potential Mie scattering within human age-related nuclear cataracts. Previous studies restricted to the equatorial plane have shown that MLBs are rare spherical objects that are 1-4 microm in diamete...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1016/j.exer.2004.05.017

    authors: Gilliland KO,Freel CD,Johnsen S,Craig Fowler W,Costello MJ

    更新日期:2004-10-01 00:00:00

  • Hyaluronan in the interphotoreceptor matrix of the eye: species differences in content, distribution, ligand binding and degradation.

    abstract::Hyaluronan (HA) distribution in the posterior eye wall from the vitreous through the sclera, with special consideration to localization in the retina and interphotoreceptor matrix (IPM), was evaluated in human, bovine, guinea pig, dog, rat and mouse tissues using a specific probe for HA (bHABC, biotinylated hyaluronan...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1006/exer.1997.0422

    authors: Hollyfield JG,Rayborn ME,Tammi M,Tammi R

    更新日期:1998-02-01 00:00:00

  • Developmental change of distribution of beta-galactoside alpha 2,6-sialyltransferase mRNA in rat retina.

    abstract::A substantial change in the glycoconjugates of the rat interphotoreceptor matrix (IPM) has recently been shown to occur between post-natal day (P) 14 and P16 in rat retinas using lectin histochemistry. This suggests that the sialic acid content on the terminus of N-glycoside linked carbohydrate chains of the IPM incre...

    journal_title:Experimental eye research

    pub_type: 杂志文章

    doi:10.1006/exer.1993.1013

    authors: Uehara F,Ohba N,Nakashima Y,Yanagita T,Ozawa M,Muramatsu T

    更新日期:1993-01-01 00:00:00