title: Rofecoxib inhibits retinal neovascularization via down regulation of cyclooxygenase-2 and vascular endothelial growth factor expression.
abstract: BACKGROUND
  To explore the anti-angiogenesis mechanism of Rofecoxib and determine whether Rofecoxib can be a therapeutic agent for the prevention of retinal neovascularization using a model of retinopathy of prematurity (ROP).
  
  
  METHODS
  ROP was induced by exposing mice to 75% oxygen from postnatal day 7 (P7 ) to P12 , then to room air from P12 to P17 . Sixteen mice were in each of the three groups: untreated ROP group as positive control, Rofecoxib-treated ROP group and the normal group (age-matched mice maintained in room air from birth to P17 as negative control). The localized expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) protein and mRNA in retinal blood vessels was assessed using immunohistochemistry, Western blot analysis and reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Mice in the Rofecoxib-treated group had a significantly reduced retinal neovascular tufts compared with those in the untreated ROP group. COX-2 and VEGF protein and mRNA expression levels were increased in the untreated ROP group, compared with the normal group. Rofecoxib decreased retinal angiogenesis by inhibiting COX-2 and VEGF expression. The expression levels of VEGF and COX-2 were positively correlated at mRNA and protein levels.
  
  
  CONCLUSIONS
  COX-2 and VEGF expressions were both involved in the regulation of angiogenesis and had the same cellular localization. Expression of COX-2 correlated positively with VEGF in retinal neovascularization. Rofecoxib attenuated retinal angiogenesis by inhibiting the expression of COX-2 and VEGF mRNA and protein.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Ning-ning
authors.initials: NN
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Yi-zhou
authors.initials: YZ
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D007783:Lactones / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D015861:Retinal Neovascularization / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D012171:Retinal Vessels / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013450:Sulfones / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D012333:RNA, Messenger; D013450:Sulfones; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C116926:rofecoxib; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: Rofecoxib; retinal neovascularization; vascular endothelial growth factor