Document Detail


The role of PGE2 receptor EP4 in pathologic ocular angiogenesis.
MedLine Citation:
PMID:  19494202     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Susan E Yanni; Joshua M Barnett; Monika L Clark; John S Penn
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-06-03
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  50     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-03     Completed Date:  2009-12-04     Revised Date:  2009-12-18    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5479-86     Citation Subset:  IM    
Affiliation:
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
EY01826/EY/NEI NIH HHS; EY07533/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
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

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