title: Tissue Plasminogen Activator as an Antiangiogenic Agent in Experimental Laser-Induced Choroidal Neovascularization in Mice.
abstract: OBJECTIVE
  We investigate the antiangiogenic efficacy of tissue plasminogen activator (tPA) on experimental laser-induced choroidal neovascularization (CNV) in mice.
  
  
  METHODS
  After CNV was induced by laser photocoagulation in 92 C57BL/6J wild-type mice, tPA (4 or 40 international units [IU]/μl) or PBS was injected intravitreally immediately after laser injury. Fluorescein angiography was performed on day 7 to grade CNV leakage. The CNV volume was measured by confocal microscopy in eyes enucleated 7 days after laser injury. Immunohistochemical studies were performed 3 days after laser injury to evaluate fibrin/fibrinogen and CD31 expression. The possible adverse effects of tPA were assessed by electroretinography (ERG) and histology on day 7.
  
  
  RESULTS
  Intravitreal administration of tPA significantly suppressed CNV leakage and CNV volume in a dose-dependent manner (P < 0.01). Intravitreal injection of tPA suppressed fibrin/fibrinogen and CD31 expression in laser-induced lesions. Histologic examination and ERG showed no evidence of retinal toxicity in eyes injected with tPA.
  
  
  CONCLUSIONS
  Intravitreal injection of tPA suppressed fibrin/fibrinogen expression and laser-induced CNV. The current results suggested that tPA may be a potential therapeutic adjuvant for treating CNV.
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ozone
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizutani
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Nozaki
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ohbayashi
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Hasegawa
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Kato
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yasukawa
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ogura
mesh_terms: D000818:Animals; D002829:Choroid / Q000000981:diagnostic imaging* / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D005337:Fibrin / Q000096:biosynthesis; D005340:Fibrinogen / Q000096:biosynthesis; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D058449:Intravitreal Injections; D017075:Laser Coagulation / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D012160:Retina / Q000000981:diagnostic imaging* / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
chemical_list: D005343:Fibrinolytic Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D005337:Fibrin; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator