scholarly journals Inhibition of Advanced Glycation and Absence of Galectin-3 Prevent Blood-Retinal Barrier Dysfunction during Short-Term Diabetes

2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
Paul Canning ◽  
Josephine V. Glenn ◽  
Daniel K. Hsu ◽  
Fu-Tong Liu ◽  
Tom A. Gardiner ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Advanced Glycation ◽  
Barrier Dysfunction ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Blood Retinal Barrier ◽  
Diabetic Retina ◽  
Retinal Microvasculature ◽  
Galectin 3 ◽  
Acute Diabetes

Breakdown of the inner blood-retinal barrier (iBRB) occurs early in diabetes and is central to the development of sight-threatening diabetic macular edema (DME) as retinopathy progresses. In the current study, we examined how advanced glycation end products (AGEs) forming early in diabetes could modulate vasopermeability factor expression in the diabetic retina and alter inter-endothelial cell tight junction (TJ) integrity leading to iBRB dysfunction. We also investigated the potential for an AGE inhibitor to prevent this acute pathology and examined a role of the AGE-binding protein galectin-3 (Gal-3) in AGE-mediated cell retinal pathophysiology. Diabetes was induced in C57/BL6 wild-type (WT) mice and in Gal-3−/−transgenic mice. Blood glucose was monitored and AGE levels were quantified by ELISA and immunohistochemistry. The diabetic groups were subdivided, and one group was treated with the AGE-inhibitor pyridoxamine (PM) while separate groups of WT and Gal-3−/−mice were maintained as nondiabetic controls. iBRB integrity was assessed by Evans blue assay alongside visualisation of TJ protein complexes via occludin-1 immunolocalization in retinal flat mounts. Retinal expression levels of the vasopermeability factor VEGF were quantified using real-time RT-PCR and ELISA. WT diabetic mice showed significant AGE -immunoreactivity in the retinal microvasculature and also showed significant iBRB breakdown (P<.005). These diabetics had higher VEGF mRNA and protein expression in comparison to controls (P<.01). PM-treated diabetics had normal iBRB function and significantly reduced diabetes-mediated VEGF expression. Diabetic retinal vessels showed disrupted TJ integrity when compared to controls, while PM-treated diabetics demonstrated near-normal configuration. Gal-3−/−mice showed significantly less diabetes-mediated iBRB dysfunction, junctional disruption, and VEGF expression changes than their WT counterparts. The data suggests an AGE-mediated disruption of iBRB via upregulation of VEGF in the diabetic retina, possibly modulating disruption of TJ integrity, even after acute diabetes. Prevention of AGE formation or genetic deletion of Gal-3 can effectively prevent these acute diabetic retinopathy changes.

PC7 ADVANCED GLYCATION ENDPRODUCT-INDUCED BREAKDOWN OF THE BLOOD RETINAL BARRIER IS MEDIATED BY GALECTIN 3

2004 ◽  
Vol 11 (6) ◽  
pp. 541-541
Author(s):  
P. Canning ◽  
N. Quinn ◽  
C. Boyle ◽  
F. -T. Liu ◽  
D. K. Hsu ◽  
...  
Keyword(s):  
Advanced Glycation ◽  
Blood Retinal Barrier ◽  
Advanced Glycation Endproduct ◽  
Galectin 3

Advanced Glycation End Products Induce Blood–Retinal Barrier Dysfunction in Normoglycemic Rats

2000 ◽  
Vol 3 (6) ◽  
pp. 380-388 ◽  
Author(s):  
Alan W. Stitt ◽  
Tisha Bhaduri ◽  
C.B.Tara McMullen ◽  
Thomas A. Gardiner ◽  
Desmond B. Archer
Keyword(s):  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Barrier Dysfunction ◽  
Blood Retinal Barrier ◽  
Glycation End Products ◽  
End Products

scholarly journals Adenosine upregulates VEGF expression in cultured myocardial vascular smooth muscle cells

1999 ◽  
Vol 277 (2) ◽  
pp. H595-H602 ◽  
Author(s):  
Jian-Wei Gu ◽  
Ann L. Brady ◽  
Vivek Anand ◽  
Michael C. Moore ◽  
Whitney C. Kelly ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mrna Expression ◽  
Vascular Smooth Muscle Cells ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Vegf Mrna Expression ◽  
Vegf Protein

We tested whether adenosine has differential effects on vascular endothelial growth factor (VEGF) expression under normoxic and hypoxic conditions, and whether A1 or A2 receptors (A1R; A2R) mediate these effects. Myocardial vascular smooth muscle cells (MVSMCs) from dog coronary artery were exposed to hypoxia (1% O2) or normoxia (20% O2) in the absence and presence of adenosine agonists or antagonists for 18 h. VEGF protein levels were measured in media with ELISA. VEGF mRNA expression was determined with Northern blot analysis. Under normoxic conditions, the adenosine A1R agonists, N 6-cyclopentyladenosine and R(-)- N 6-(2-phenylisopropyl)adenosine did not increase VEGF protein levels at A1R stimulatory concentrations. However, adenosine (5 μM) and the adenosine A2R agonist N 6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)]ethyl adenosine (DPMA; 100 nM) increased VEGF protein levels by 51 and 132% and increased VEGF mRNA expression by 44 and 90%, respectively, in cultured MVSMCs under normoxic conditions. Hypoxia caused an approximately fourfold increase in VEGF protein and mRNA expression, which could not be augmented with exogenous adenosine, A2R agonist (DPMA), or A1R agonist [1,3-diethyl-8-phenylxanthine (DPX)]. The A2R antagonist 8-(3-chlorostyryl)-caffeine completely blocked adenosine-induced VEGF protein and mRNA expression and decreased baseline VEGF protein levels by up to ∼60% under normoxic conditions but only by ∼25% under hypoxic conditions. The A1R antagonist DPX had no effect. These results are consistent with the hypothesis that 1) adenosine increases VEGF protein and mRNA expression by way of A2R. 2) Adenosine plays a major role as an autocrine factor regulating VEGF expression during normoxic conditions but has a relatively minor role during hypoxic conditions. 3) Endogenous adenosine can account for the majority of basal VEGF secretion by MVSMCs under normoxic conditions and could therefore be a maintenance factor for the vasculature.

scholarly journals Mineralocorticoid receptor pathway and its antagonism in a model of diabetic retinopathy

2021 ◽  
Author(s):  
Min Zhao ◽  
Emmanuelle Gelize ◽  
Rinath Levy ◽  
Alexandre Moulin ◽  
Frédéric Azan ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Mineralocorticoid Receptor ◽  
Vision Loss ◽  
Therapeutic Option ◽  
Lipocalin 2 ◽  
Gk Rats ◽  
Diabetic Retina ◽  
Pathway Activation ◽  
Genes Encoding ◽  
Galectin 3

<p>Diabetic retinopathy remains a major cause of vision loss worldwide. Mineralocorticoid receptor (MR) pathway activation contributes to diabetic nephropathy but its role in retinopathy is unknown. In this study, we show that MR is overexpressed in the retina of type 2 diabetic Goto-Kakizaki (GK) rats and humans and, that cortisol is the MR ligand in human eyes. Lipocalin 2 and galectin 3, two biomarkers of diabetic complications regulated by MR are increased in GK and human retina. The sustained intraocular delivery of spironolactone, a steroidal mineralocorticoid antagonist, decreased the early and late pathogenic features of retinopathy in GK rats, such as retinal inflammation, vascular leakage and retinal edema through the up-regulation of genes encoding proteins known to intervene in vascular permeability such as <i>Hey1, Vldlr</i>, <i>Pten</i>, <i>Slc7a1, Tjp1, Dlg1 and Sesn2 </i>but did not decrease VEGF. Spironolactone also normalized the distribution of ion and water channels in macroglial cells. These results indicate that MR is activated in GK and human diabetic retina and that local MR antagonism could be a novel therapeutic option for diabetic retinopathy.</p>

Intraocular exosomes in eye diseases

2021 ◽  
Vol 21 ◽  
Author(s):  
Hui Zhang ◽  
Xiaomin Zhang ◽  
Xiaorong Li
Keyword(s):  
Messenger Rna ◽  
Biological Fluids ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Pathological State ◽  
Barrier Dysfunction ◽  
Blood Retinal Barrier ◽  
Ecm Remodeling ◽  
Age Related ◽  
Eye Tissues

: Exosomes, nanosized extracellular vesicles with a size of 30–150nm, contain many biological materials, such as messenger RNA (mRNA), microRNA (miRNA), proteins, and transcription factors. It has been identified in all biological fluids and recognized as an important part of intercellular communication. While the role of exosomes in cancer has been studied in-depth, our understanding of their relevance for ocular tissues has just begun to evolve. Intraocular fluids, including aqueous humor and vitreous humor, play a role in nourishing eye tissues and in expelling metabolites. In the pathological state, intraocular exosomes can mediate pathological processes such as ECM remodeling, retinal inflammation, and blood-retinal barrier dysfunction. Herein, we reviewed the latest advances of intraocular exosomes in the research of several eye diseases, including glaucoma, age-related macular degeneration, myopia, and ocular tumors, and discuss how intraocular exosomes contribute to the pathogenesis and progression of multiple eye diseases.

scholarly journals C-reactive protein isoforms differentially affect outer blood-retinal barrier integrity and function

2017 ◽  
Vol 312 (3) ◽  
pp. C244-C253 ◽  
Author(s):  
Blanca Molins ◽  
Anna Pascual ◽  
Méndez ◽  
Victor Llorenç ◽  
Javier Zarranz-Ventura ◽  
...  
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Protein Isoforms ◽  
Age Related Macular Degeneration ◽  
C Reactive Protein ◽  
Barrier Dysfunction ◽  
Blood Retinal Barrier ◽  
Reactive Protein ◽  
Anti Vegf ◽  
Age Related

The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier (oBRB) and is the prime target of early age-related macular degeneration (AMD). C-reactive protein (CRP), a serum biomarker for chronic inflammation and AMD, presents two different isoforms, monomeric (mCRP) and pentameric (pCRP), that may have a different effect on inflammation and barrier function in the RPE. The results reported in this study suggest that mCRP but not pCRP impairs RPE functionality by increasing paracellular permeability and disrupting the tight junction proteins ZO-1 and occludin in RPE cells. Additionally, we evaluated the effect of drugs commonly used in clinical settings on mCRP-induced barrier dysfunction. We found that a corticosteroid (methylprednisolone) and an anti-VEGF agent (bevacizumab) prevented mCRP-induced ARPE-19 barrier disruption and IL-8 production. Furthermore, bevacizumab was also able to revert mCRP-induced IL-8 increase after mCRP stimulation. In conclusion, the presence of mCRP within retinal tissue may lead to disruption of the oBRB, an effect that may be modified in the presence of corticosteroids or anti-VEGF drugs.

scholarly journals VEGF, VEGF165b and EG-VEGF expression is specifically related with hormone profile in pituitary adenomas

2019 ◽  
Vol 63 (1) ◽  
Author(s):  
Ana Silvia Corlan ◽  
Anca Maria Cîmpean ◽  
Eugen Melnic ◽  
Marius Raica ◽  
Simona Sarb
Keyword(s):  
Pituitary Adenomas ◽  
P Value ◽  
Endocrine Gland ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Folliculostellate Cells ◽  
Hormone Profile ◽  
Hormonal Milieu ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.

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