Cyclooxygenase-2 in human and experimental ischemic proliferative retinopathy.
Details
State: Public
Version: Final published version
Serval ID
serval:BIB_3A50A6EB875D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cyclooxygenase-2 in human and experimental ischemic proliferative retinopathy.
Journal
Circulation
ISSN
1524-4539 (Electronic)
ISSN-L
0009-7322
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
108
Number
2
Pages
198-204
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
BACKGROUND: Intravitreal neovascular diseases, as in ischemic retinopathies, are a major cause of blindness. Because inflammatory mechanisms influence vitreal neovascularization and cyclooxygenase (COX)-2 promotes tumor angiogenesis, we investigated the role of COX-2 in ischemic proliferative retinopathy.
METHODS AND RESULTS: We describe here that COX-2 is induced in retinal astrocytes in human diabetic retinopathy, in the murine and rat model of ischemic proliferative retinopathy in vivo, and in hypoxic astrocytes in vitro. Specific COX-2 but not COX-1 inhibitors prevented intravitreal neovascularization, whereas prostaglandin E2, mainly via its prostaglandin E receptor 3 (EP3), exacerbated neovascularization. COX-2 inhibition induced an upregulation of thrombospondin-1 and its CD36 receptor, consistent with the observed antiangiogenic effects of COX-2 inhibition; EP3 stimulation reversed effects of COX-2 inhibitors on thrombospondin-1 and CD36.
CONCLUSIONS: These findings point to an important role for COX-2 in ischemic proliferative retinopathy, as in diabetes.
METHODS AND RESULTS: We describe here that COX-2 is induced in retinal astrocytes in human diabetic retinopathy, in the murine and rat model of ischemic proliferative retinopathy in vivo, and in hypoxic astrocytes in vitro. Specific COX-2 but not COX-1 inhibitors prevented intravitreal neovascularization, whereas prostaglandin E2, mainly via its prostaglandin E receptor 3 (EP3), exacerbated neovascularization. COX-2 inhibition induced an upregulation of thrombospondin-1 and its CD36 receptor, consistent with the observed antiangiogenic effects of COX-2 inhibition; EP3 stimulation reversed effects of COX-2 inhibitors on thrombospondin-1 and CD36.
CONCLUSIONS: These findings point to an important role for COX-2 in ischemic proliferative retinopathy, as in diabetes.
Keywords
Adult, Aged, Animals, Antigens, CD36/metabolism, Astrocytes/drug effects, Astrocytes/enzymology, Cell Division/drug effects, Cells, Cultured, Cyclooxygenase 2, Diabetic Retinopathy/complications, Diabetic Retinopathy/drug therapy, Dinoprostone/metabolism, Disease Models, Animal, Endothelial Growth Factors/metabolism, Enzyme Inhibitors/pharmacology, Female, Humans, Intercellular Signaling Peptides and Proteins/metabolism, Ischemia/complications, Ischemia/enzymology, Isoenzymes/antagonists & inhibitors, Isoenzymes/metabolism, Lymphokines/metabolism, Male, Membrane Proteins, Mice, Mice, Inbred C57BL, Middle Aged, Neovascularization, Pathologic/drug therapy, Neovascularization, Pathologic/pathology, Prostaglandin-Endoperoxide Synthases/metabolism, Rats, Rats, Sprague-Dawley, Receptors, Immunologic, Receptors, Lipoprotein/metabolism, Receptors, Prostaglandin E/drug effects, Receptors, Prostaglandin E/metabolism, Receptors, Prostaglandin E, EP3 Subtype, Receptors, Prostaglandin E, EP4 Subtype, Receptors, Scavenger, Retina/drug effects, Retina/enzymology, Retinal Vessels/drug effects, Retinal Vessels/pathology, Thrombospondin 1/metabolism, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2/metabolism, Vascular Endothelial Growth Factors, Vitreoretinopathy, Proliferative/complications, Vitreoretinopathy, Proliferative/drug therapy
Pubmed
Web of science
Open Access
Yes
Create date
21/03/2014 10:12
Last modification date
20/08/2019 14:29
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