title: Celecoxib attenuates retinal angiogenesis in a mouse model of oxygen-induced retinopathy.
abstract: This study aimed to investigate the anti-angiogenic effects of Celecoxib on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible transcription factor 1α (HIF-1α) in a mouse model for oxygen-induced retinopathy (OIR). The OIR mice were exposed to 75% oxygen from postnatal day 7 (P7) to P12, after which the mice were randomly assigned to two groups (Celecoxib and vehicle) and were brought to room air for additional five days. Celecoxib or vehicle was administered from P12 to P17. Age-matched mice maintained in room air from birth to P17 were administered vehicle from P12 to P17 (RA group). Blood vessel profiles in the retina were used to count by histologic methods. Retina protein and mRNA of VEGF and HIF-1α were assessed by immunohistochemistry, western-blot and RT-PCR. Compared with the RA group, the OIR mice exhibited over-expression in VEGF and HIF-1α mRNA and protein. In addition, they had a positive and spatial correlation. Celecoxib- treated OIR mice reduced the retinal neovascular tufts and the levels of VEGF and HIF-1α. These data suggest that Celecoxib inhibits retinal pathogenic angiogenesis through down-regulating HIF-1α expression which suppressing VEGF transcription. Celecoxib could potentially serve as a portent pharmaceutical agent to inhibit retinal angiogenesis.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of China Medical University Shenyang, Liaoning Province, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of China Medical University Shenyang, Liaoning Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of China Medical University Shenyang, Liaoning Province, China.
authors.forename: Na
authors.initials: N
authors.lastname: Cai
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000068579:Celecoxib / Q000494:pharmacology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010100:Oxygen; D012333:RNA, Messenger / Q000378:metabolism; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000068579:Celecoxib; D010100:Oxygen
keywords: Hypoxia-inducible factor-1α; a selective cyclooxygenase-2 inhibitor; retinal neovascularization; vascular endothelial growth factor