title: The effect of selective cyclooxygenase-2 inhibitor on corneal angiogenesis in the rat.
abstract: OBJECTIVE
  Eicosanoids that are present in inflamed tissues are thought to play a significant role in angiogenesis. Cyclooxygenase, a key enzyme in eicosanoid synthesis, has recently been shown to exist in two isoforms: the constitutive COX-1 and the inducible COX-2. This study was undertaken to determine the role of COX-2 in the corneal angiogenic response.
  
  
  METHODS
  Angiogenesis in the rat cornea was provoked by chemical cautery. Either NS-398, a selective COX-2 inhibitor, or indomethacin, a non-selective COX inhibitor, was applied topically 3 times daily for 4 days. Neovascularization was quantitated by digital image analysis in corneal flat preparations. To test their inhibitory effects on eicosanoid synthesis, normal or cauterized corneas were incubated in the culture medium with the inhibitor. Prostaglandin E2 in the medium was assayed using an enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Both NS-398 and indomethacin significantly inhibited corneal neovascularization with the % inhibition of 36.4 +/- 9.6%, and 38.5 +/- 9.0%, respectively, when applied topically at a concentration of 0.1% (p <.001). Neither reduced the angiogenic response at a concentration of 0.01% or below. PGE(2) production in the cauterized cornea was 2.0 times higher than that in the controls. In normal corneas, indomethacin inhibited PGE(2) synthesis by 80%, whereas NS-398 inhibited it by no more than 20%. In contrast, in injured corneas, both indomethacin and NS-398 inhibited PGE(2) synthesis in a similar fashion, with a maximal inhibition rate of 75 to 80%.
  
  
  CONCLUSIONS
  Our results suggest that COX-2 induction in cauterized corneas increases the level of eicosanoids, which result in corneal angiogenesis.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo,Japan. yamadam@ned.keio.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Kawai
authors.forename: Y
authors.initials: Y
authors.lastname: Kawai
authors.forename: Y
authors.initials: Y
authors.lastname: Mashima
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin