title: Inhibitory effects of the platelet-activating factor receptor antagonists, CV-3988 and Ginkgolide B, on alkali burn-induced corneal neovascularization.
abstract: OBJECTIVE
  Platelet-activating factor (PAF) has been found in various ocular tissues; the activity of PAF depends on the binding to its specific receptor, PAF-receptor. We investigated the therapeutic effects of PAF-receptor antagonists (CV-3988 and Ginkgolide B) on alkali burn-induced corneal neovascularization (CNV).
  
  
  METHODS
  CNV was induced by applying a 0.2 N sodium hydroxide (3 µl, NaOH) solution directly on mice corneas. CV-3988 (1 mM/10 µl) and Ginkgolide B (1 mM/10 µl) were administered topically on the corneas three times daily for three consecutive days. CNV was evaluated under a slit-lamp microscope. Corneas were processed for histological, immunohistochemical and reverse transcription polymerase chain reaction analysis. Human umbilical vein endothelial cells were used for the migration and tube formation assay.
  
  
  RESULTS
  Application of CV-3988 and Ginkgolide B inhibited CNV caused by alkali burn. CV-3988 and Ginkgolide B attenuated the expression of PAF-receptor mRNA. Alkali injury induced a massively increased intraocular mRNA expression of an angiogenic factor in cornea tissues, whereas these increments were attenuated by the application of CV-3988 and Ginkgolide B.
  
  
  CONCLUSIONS
  CV-3988 and Ginkgolide B reversed opacity and neovascularization in alkali burn-induced corneas. Our findings suggest that CV-3988 and Ginkgolide B may be therapeutically useful in the treatment of CNV and inflammation.
authors.affiliation: Department of Internal Medicine, Pulmonary and Critical Care Medicine , New Haven, CT , USA .
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.forename: Giyoun
authors.initials: G
authors.lastname: Na
authors.forename: Dae-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Sae-Gwang
authors.initials: SG
authors.lastname: Park
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Yang
authors.forename: Sung Su
authors.initials: SS
authors.lastname: Yea
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Lee
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
mesh_terms: D000468:Alkalies / Q000009:adverse effects; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D065306:Corneal Injuries / Q000139:chemically induced; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D003318:Corneal Opacity / Q000188:drug therapy; D005126:Eye Burns / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D046934:Ginkgolides / Q000494:pharmacology / Q000627:therapeutic use*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D010742:Phospholipid Ethers / Q000494:pharmacology / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000468:Alkalies; D046934:Ginkgolides; D007783:Lactones; D010742:Phospholipid Ethers; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C037913:CV 3988; C045856:ginkgolide B
keywords: Corneal neovascularization; opacity; pigment epithelium-derived factor; platelet-activating factor; vascular endothelial growth factor