| VEGF modulation of retinal pigment epithelium resistance. | |
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MedLine Citation:
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PMID: 17915218 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Fluid accumulation into the subretinal space and the development of macular edema is a common condition in age-related macular degeneration, diabetic retinopathy, and following ocular surgery, or injury. Vascular endothelial growth factor (VEGF) and other cytokines have been implicated in the disruption of retinal pigment epithelium (RPE) barrier function and a reduction in the regulated removal of subretinal fluid; however, the cellular and molecular events linking these agents to the disruption of barrier function have not been established. In the current study, cultures of ARPE-19 and primary porcine retinal pigment epithelium (RPE) cells were utilized to investigate the effects of the VEGF-induced modifications to the barrier properties of the RPE. The barrier function was determined by transepithelial resistance (TER) measurements and morphology of the RPE monolayers. In both ARPE-19 and primary porcine RPE cells the administration of VEGF produced a significant drop in TER, and this response was only observed following apical administration. Maximum reduction in TER was reached 5h post VEGF administration. These responses were concentration-dependent with an EC(50) of 502pg/mL in ARPE-19 cells and 251pg/mL in primary porcine cells. In both ARPE-19 and primary RPE cells, the response to VEGF was blocked by pretreatment with the relatively selective VEGF-R2 antagonists, SU5416 or ZM323881, or the protein tyrosine kinase inhibitor, genistein. Administration of the relatively selective VEGF-R2 agonist, VEGF-E, also reduced TER in a concentration-dependent manner (EC(50) of 474pg/mL), while VEGF-R1 agonist, placental growth factor (PlGF), did not significantly alter the TER. Immunolocalization studies demonstrated that confluent monolayers exhibited continuous cell-to-cell ZO-1 protein contacts and apical localization of the VEGF-R2 receptors. These data provide evidence that the VEGF-induced breakdown of RPE barrier function is mediated by the activation of apically-oriented VEGF-R2 receptors. Thus, VEGF-mediated increases in RPE permeability are initiated by a rise in intraocular levels of VEGF. |
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Authors:
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Zsolt Ablonczy; Craig E Crosson |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-08-24 |
Journal Detail:
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Title: Experimental eye research Volume: 85 ISSN: 0014-4835 ISO Abbreviation: Exp. Eye Res. Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-12-06 Completed Date: 2008-02-15 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0370707 Medline TA: Exp Eye Res Country: England |
Other Details:
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Languages: eng Pagination: 762-71 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA. ablonczy@musc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Cell Membrane Permeability / drug effects Cells, Cultured Dose-Response Relationship, Drug Electric Impedance Humans Indoles / pharmacology Pigment Epithelium of Eye / drug effects*, physiology Pyrroles / pharmacology Quinazolines / pharmacology Retina / drug effects*, physiology Sus scrofa Tight Junctions / drug effects, physiology Vascular Endothelial Growth Factor A / pharmacology* Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors, physiology |
| Grant Support | |
ID/Acronym/Agency:
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EY 009741/EY/NEI NIH HHS; EY 014793/EY/NEI NIH HHS; EY 13520/EY/NEI NIH HHS; R01 EY009741-15/EY/NEI NIH HHS; R24 EY014793-01/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Indoles; 0/Pyrroles; 0/Quinazolines; 0/SU 5416; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 0/ZM323881; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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