| The role of PGE2 receptor EP4 in pathologic ocular angiogenesis. | |
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MedLine Citation:
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PMID: 19494202 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: PGE(2) binds to PGE(2) receptors (EP(1-4)). The purpose of the present study was to investigate the role of the EP(4) receptor in angiogenic cell behaviors of retinal Müller cells and retinal microvascular endothelial cells (RMECs) and to assess the efficacy of an EP(4) antagonist in rat models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (LCNV). METHODS: Müller cells derived from COX-2-null mice were treated with increasing concentrations of the EP(4) agonist PGE(1)-OH, and wild-type Müller cells were treated with increasing concentrations of the EP(4) antagonist L-161982; VEGF production was assessed. Human RMECs (HRMECs) were treated with increasing concentrations of L-161982, and cell proliferation and tube formation were assessed. Rats subjected to OIR or LCNV were administered L-161982, and the neovascular area was measured. RESULTS: COX-2-null mouse Müller cells treated with increasing concentrations of PGE(1)-OH demonstrated a significant increase in VEGF production (P < or = 0.0165). Wild-type mouse Müller cells treated with increasing concentrations of L-161982 demonstrated a significant decrease in VEGF production (P < or = 0.0291). HRMECs treated with increasing concentrations of L-161982 demonstrated a significant reduction in VEGF-induced cell proliferation (P < or = 0.0033) and tube formation (P < 0.0344). L-161982 treatment significantly reduced pathologic neovascularization in OIR (P < 0.0069) and LCNV (P < or = 0.0329). CONCLUSIONS: Preliminary investigation has demonstrated that EP(4) activation or inhibition influences the behaviors of two retinal cell types known to play roles in pathologic ocular angiogenesis. These findings suggest that the EP(4) receptor may be a valuable therapeutic target in neovascular eye disease. |
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Authors:
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Susan E Yanni; Joshua M Barnett; Monika L Clark; John S Penn |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-06-03 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 50 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-11-03 Completed Date: 2009-12-04 Revised Date: 2009-12-18 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 5479-86 Citation Subset: IM |
Affiliation:
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Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Cell Proliferation / drug effects Choroid / blood supply Choroidal Neovascularization / etiology, metabolism*, prevention & control Cyclooxygenase 2 / genetics Dinoprostone / metabolism Disease Models, Animal Endothelium, Vascular / drug effects, metabolism* Enzyme-Linked Immunosorbent Assay Humans Laser Coagulation / adverse effects Male Mice Neuroglia / drug effects, metabolism* Oxygen / toxicity Rats Rats, Inbred BN Rats, Sprague-Dawley Receptors, Prostaglandin E / agonists, antagonists & inhibitors, physiology* Retinal Neovascularization / chemically induced, metabolism*, prevention & control Retinal Vessels / drug effects Thiophenes / pharmacology Triazoles / pharmacology Vascular Endothelial Growth Factor A / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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EY01826/EY/NEI NIH HHS; EY07533/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/L-161982; 0/Receptors, Prostaglandin E; 0/Thiophenes; 0/Triazoles; 0/Vascular Endothelial Growth Factor A; 0/prostaglandin E2 receptor, EP4 subtype; 0/vascular endothelial growth factor A, mouse; 363-24-6/Dinoprostone; 7782-44-7/Oxygen; EC 1.14.99.-/Ptgs2 protein, mouse; EC 1.14.99.1/Cyclooxygenase 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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