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Occludin zo-1 diabetic retinopathy

Jang-Hyuk Yun, Sung Wook Park, Kyung-Jin Kim, Jong-Sup Bae, Eun Hui Lee, Sun Ha Paek, Seung U Kim, Sangkyu Ye, Jeong-Hun Kim, Chung-Hyun Cho
Vascular inflammation is characteristic feature of diabetic retinopathy. In diabetic retina, a variety of the pro-inflammatory cytokines are elevated and involved in endothelial dysfunction. STAT3 transcription factor has been implicated in mediating cytokine signaling during vascular inflammation. However, whether and how STAT3 is involved in the direct regulation of the endothelial permeability is currently undefined. Our studies revealed that IL-6-induced STAT3 activation increases retinal endothelial permeability and vascular leakage in retinas of mice through the reduced expression of the tight junction proteins ZO-1 and occludin...
August 31, 2016: Journal of Cellular Physiology
Yang Wang, Hua Yan
Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and a major cause of blindness in the developing world. Early diabetic retinopathy is characterized by a loss of pericytes and vascular endothelial cells, a breakdown of the blood-retinal barrier, vascular dysfunction and vascular-neuroinflammation. However, optimal treatment options and related mechanisms are still unclear. MicroRNA-126 (miR-126) plays a potential role in the pathogenesis in DR, which may regulate VEGF, Ang-1 and VCAM-1 expressions...
2016: Scientific Reports
Lingling Fan, Hua Yan
PURPOSE: FTY720 has shown a protective effect in several diseases via inhibiting inflammation and decreasing vascular permeability. The purpose of this study was to assess the impact of FTY720 on inflammation and the blood-retinal barrier (BRB) in diabetic rats. METHODS: Male Wister rats were induced to develop diabetes by streptozotocin, and FTY720 was administered by oral gavage daily for 12 weeks. All experiments were performed at 12 weeks after model establishment...
March 2016: Investigative Ophthalmology & Visual Science
Shuai Wang, Shanshan Du, Qiang Wu, Jianyan Hu, Tingting Li
PURPOSE: The purpose of this study was to determine the effect of decorin on the barrier function of human retinal pigment epithelial (RPE) cells under high-glucose (HG) plus hypoxia conditions. METHODS: Human RPE (ARPE-19) cells were cultured for 18 days in normal glucose (5.5 mM) or HG (25 mM) medium. In addition, to mimic the hypoxic impact which occurs in diabetic retinopathy, cells were treated with 100 μM CoCl2 during the last 2 days of the experiment. Decorin, 100 nM, was applied 1 hour before CoCl2 was added...
May 2015: Investigative Ophthalmology & Visual Science
Andreia Gonçalves, Catarina Marques, Ermelindo Leal, Carlos F Ribeiro, Flávio Reis, António F Ambrósio, Rosa Fernandes
Diabetic retinopathy, a leading cause of vision loss in working-age population, is often associated with inflammation and apoptosis. We have previously reported that sitagliptin, a DPP-IV inhibitor, exerts beneficial effects in the retina of type 2 diabetic animals. The present study aimed to evaluate whether sitagliptin can exert protective effects in the retina of type 1 diabetic animals by a mechanism independent of insulin secretion and glycemia normalization. Streptozotocin-induced diabetic rats were treated orally with sitagliptin (5mg/kg/day) for the last two weeks of 4 weeks of diabetes...
September 2014: Biochimica et Biophysica Acta
Maria C Bewley, Brian R Tash, Fang Tian, John M Flanagan
Tight junctions (TJs) are protein complexes comprised of claudins, which anchor them in the membrane and numerous cytosolic scaffolding proteins including MAGI, MUPP1, cingulin and members of the Zonula Occludens (ZO) family. Originally, their main function was thought to be as a paracellular barrier. More recently, however, additional roles in signal transduction, differentiation and proliferation have been reported. Dysregulation is associated with a wide range of disease states, including diabetic retinopathy, irritable bowel disease and some cancers...
January 1, 2013: Tissue Barriers
Thomas Tien, Kevin F Barrette, Argyrios Chronopoulos, Sayon Roy
PURPOSE: To investigate whether high glucose (HG)-induced downregulation of connexin 43 (Cx43), a gap junction protein, alters ZO-1 and occludin expression and cell monolayer permeability. METHODS: Rat retinal endothelial cells (RRECs) were grown in normal (N; 5 mM) medium, high glucose (HG; 30 mM) medium, N medium transfected with Cx43 siRNA, or N medium transfected with scrambled siRNA. To determine Cx43, occludin, and ZO-1 protein expression, Western blot (WB) analysis and immunostaining were performed...
2013: Investigative Ophthalmology & Visual Science
Joo Young Shin, Joonhong Sohn, Kyu Hyung Park
To evaluate the effect of chlorogenic acid (CGA), a polyphenol abundant in coffee, on retinal vascular leakage in the rat model of diabetic retinopathy, Sprague-Dawley rats were divided into four groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with 10 and 20 mg/kg chlorogenic acid intraperitoneally daily for 14 days, respectively. Blood-retinal barrier (BRB) breakdown was evaluated using FITC-dextran. Vascular endothelial growth factor (VEGF) distribution and expression level was evaluated with immunohistochemistry and Western blot analysis...
April 2013: Journal of Korean Medical Science
Partha S Bhattacharjee, Tashfin S Huq, Valencia Potter, Anna Young, Ian R Davenport, Richard Graves, Tarun K Mandal, Christian Clement, Harris E McFerrin, Syed Muniruzzaman, Shubha K Ireland, James M Hill
Although the importance of human apolipoprotein E (apoE) in vascular diseases has clearly been established, most of the research on apoE has focused on its role in cholesterol metabolism. In view of the observation that apoE and its functional domains impact extracellular matrix (ECM) remodeling, we hypothesized that apoE could also confer protection against ECM degradation by mechanisms independent of its role in cholesterol and lipoprotein transport. The ECM degrading enzyme, heparanase, is secreted by cells as pro-heparanase that is internalized through low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1) to become enzymatically active...
2012: PloS One
Soraya Scuderi, Agata Grazia D'Amico, Alessandro Castorina, Rosa Imbesi, Maria Luisa Carnazza, Velia D'Agata
Breakdown of outer blood retinal barrier (BRB) due to the disruption of tight junctions (TJs) is one of the main factors accounting for diabetic macular edema (DME), a major complication of diabetic retinopathy. Previously it has been shown that PACAP and VIP are protective against several types of retinal injuries. However, their involvement in the maintenance of outer BRB function during DME remains uncovered. Here, using an in vitro model of DME, we explored the effects of both PACAP and VIP. Human retinal pigment epithelial cells (ARPE19) were cultured for 26 days either in normal glucose (5...
January 2013: Peptides
Marcus Kernt, Sarah Thiele, Raffael G Liegl, Barbara Kernt, Kirsten Eibl, Christos Haritoglou, Michael W Ulbig, Anselm Kampik
This study investigates the effects of the multikinase inhibitor axitinib on the expression of vascular endothelial growth factor (VEGF) receptors 1/2 (VEGFR-1/2) and platelet-derived growth factor (PDGF) receptor beta (PDGFR-β), hypoxia-induced increased tissue permeability, occludin, zonula occludens protein 1 (ZO-1), VEGF-A, and PDGF expression of human retinal pigment epithelial (RPE) cells and human umbilical vein endothelial cells (HUVECs). Primary human RPE cells and HUVECs were exposed to hypoxia and axitinib...
February 2012: Growth Factors
Marta Garcia-Ramírez, Marta Villarroel, Lídia Corraliza, Cristina Hernández, Rafael Simó
The retinal pigment epithelium (RPE) is a specialized epithelium lying in the interface between the -neural retina and the choriocapillaris where it forms the outer blood-retinal barrier (BRB). The tight junctions (TJ)s expressed in the outer BRB control fluids and solutes that enter the retina and this sealing function, which is essential for the retinal homeostasis, is impaired in diabetic retinopathy. In this -chapter, we provide the methods to explore the function of the RPE barrier by measuring Transepithelial electrical resistance (TER) and paracellular permeability to dextran in cultures of ARPE-19 cells (an immortalized RPE cell line)...
2011: Methods in Molecular Biology
Ermelindo C Leal, João Martins, Paula Voabil, Joana Liberal, Carlo Chiavaroli, Jacques Bauer, José Cunha-Vaz, António F Ambrósio
OBJECTIVE: Calcium dobesilate (CaD) has been used in the treatment of diabetic retinopathy in the last decades, but its mechanisms of action are not elucidated. CaD is able to correct the excessive vascular permeability in the retina of diabetic patients and in experimental diabetes. We investigated the molecular and cellular mechanisms underlying the protective effects of CaD against the increase in blood-retinal barrier (BRB) permeability induced by diabetes. RESEARCH DESIGN AND METHODS: Wistar rats were divided into three groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with CaD...
October 2010: Diabetes
Marta Villarroel, Marta García-Ramírez, Lidia Corraliza, Cristina Hernández, Rafael Simó
INTRODUCTION: One of the early features of diabetic retinopathy is the breakdown of the blood-retinal barrier (BRB) due to disruption of the tight junctions. Whereas impairment of the proteins involved in the disruption of the tight junctions of the internal BRB has been extensively studied, there is no information on the direct effect of high glucose concentration on the barrier function of the outer blood-retinal barrier (formed by the retinal pigment epithelium [RPE]). The aim of this study was to explore the effect of high glucose concentration on the expression of tight junction proteins (occludin, zonula occludens-1 [ZO-1] and claudin-1) in a human RPE line under two distinct glucose concentrations...
February 2009: Endocrinología y Nutrición: órgano de la Sociedad Española de Endocrinología y Nutrición
Claudio Bucolo, Keith W Ward, Emanuela Mazzon, Salvatore Cuzzocrea, Filippo Drago
PURPOSE: Retinal microvascular cells play a crucial role in the pathogenesis of diabetic retinopathy. The endothelial effects of cloricromene, a novel coumarin derivative, on diabetic retinopathy induced by streptozotocin (STZ) in the rat were investigated. METHODS: Cloricromene (10 mg/kg intraperitoneally) was administered daily in diabetic rats, and 60 days later eyes were enucleated for localization of nitrotyrosine, ICAM-1, VEGF, ZO-1, occludin, claudin-5, and VE-cadherin by immunohistochemical analysis...
August 2009: Investigative Ophthalmology & Visual Science
H L Deissler, G E Lang
BACKGROUND: VEGF signalling is deregulated in diabetic retinopathy. Therefore, VEGF inhibitors like the modified RNA-oligonucleotide pegaptanib (VEGF aptamer, Macugen) which inhibits the interaction of VEGF(165) with its receptors, are currently being discussed as therapeutic options in the treatment of diabetic retinopathy. VEGF(165) does not only stimulate the proliferation and migration of endothelial cells but also induces delocalization of occludin which is part of the so-called tight junctions of endothelial cells likely associated with the breakdown of the blood-retina barrier...
October 2008: Klinische Monatsblätter Für Augenheilkunde
H Deissler, H Deissler, S Lang, G E Lang
BACKGROUND: Because vascular endothelial growth factor (VEGF) signalling is deregulated in diabetic retinopathy, the potential therapeutic effects of VEGF inhibitors such as the human VEGF-specific antibody ranibizumab are currently being tested. A study was undertaken to determine whether VEGF-stimulated processes in retinal endothelial cells are reversed by ranibizumab. METHODS: The influence of VEGF(121) and VEGF(165) on the proliferation and migration of immortalised bovine retinal endothelial cells (iBREC) was studied in the presence and absence of ranibizumab...
June 2008: British Journal of Ophthalmology
Ermelindo C Leal, Ayyakkannu Manivannan, Ken-Ichi Hosoya, Tetsuya Terasaki, José Cunha-Vaz, António Francisco Ambrósio, John V Forrester
PURPOSE: Nitric oxide (NO) is involved in leukostasis and blood-retinal barrier (BRB) breakdown in the early stages of diabetic retinopathy (DR), but it is unclear which NO synthase (NOS) isoforms are primarily involved. In this study, the authors aimed to clarify the involvement of constitutive (eNOS, nNOS) and inducible NOS (iNOS) isoforms and the mechanisms underlying NO-mediated leukostasis and BRB breakdown. METHODS: Diabetes was induced with streptozotocin for 2 weeks...
November 2007: Investigative Ophthalmology & Visual Science
Nicole S Harhaj, David A Antonetti
The mechanism by which epithelial and endothelial cells interact to form polarized tissue is of fundamental importance to multicellular organisms. Dysregulation of these barriers occurs in a variety of diseases, destroying the normal cellular environments and leading to organ failure. Increased levels of growth factors are a common characteristic of diseases exhibiting tissue permeability, suggesting that growth factors play a direct role in elevating permeability. Of particular concern for this laboratory, increased expression of vascular endothelial growth factor may enhance vascular permeability in diabetic retinopathy, leading to vision impairment and blindness...
July 2004: International Journal of Biochemistry & Cell Biology
Nicole S Harhaj, Alistair J Barber, David A Antonetti
Increased tissue permeability is a common characteristic of a number of diseases such as pulmonary edema, inflammatory bowel disease, several kidney diseases, diabetic retinopathy, and tumors. We hypothesized that growth factors increase permeability by redistribution of tight junction proteins away from the cell border. To investigate mechanisms of growth factor-mediated permeability, we examined the effect of platelet derived growth factor (PDGF) on Madin-Darby canine kidney (MDCK) cell tight junction protein distribution and on permeability...
December 2002: Journal of Cellular Physiology
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