title: Inhibition of choroidal neovascularization in rats by the urokinase-derived peptide A6.
abstract: OBJECTIVE
  To evaluate the inhibitory effects of a urokinase-derived octapeptide A6 on laser-induced choroidal neovascularization (CNV).
  
  
  METHODS
  In the first arm of the study, subcutaneous injection of A6 (200 mg/kg per day) into the right eyes in 20 rats and phosphate-buffered saline in 20 control rats was started 1 day before laser injury. Angiography was performed at week 2. To evaluate the dose response, a second arm of the study was performed in the left eyes. Half of the treatment group was treated with 400 mg/kg per day, and the remaining half continued to receive 200 mg/kg per day beginning on week 4. Laser injury was made at week 5 and angiography was performed at week 7. Angiographic evaluation, histopathologic evaluation including maximum CNV thickness and factor-VIII-stained endothelium counting were performed in the second arm of the study. Choroidal concentrations of A6 were measured.
  
  
  RESULTS
  In the first arm of the study, angiography showed a 40.8% reduction in CNV in the 200-mg/kg per day treatment group, compared with the control (P = 0.0008). In the second arm of the study, angiographic reduction in CNV was 37.9% in the 200-mg/kg per day group (P = 0.0314) and 70.0% in the 400-mg/kg per day group (P = 0.0124), compared with the control. CNV was significantly less in the 400-mg/kg per day group than in the 200-mg/kg per day group (P = 0.0393). Both CNV thickness and number of endothelial cells were reduced in a dose-dependent manner and significantly less than in the control (P < 0.05). Mean choroidal concentration of A6 2 hours after injection was 0.72 micro M in the 200-mg/kg per day (100 mg/kg every 12 hours) and 1.75 micro M in the 400-mg/kg per day (200 mg/kg every 12 hours) treatment groups. Levels at 11 hours after injections were undetectable.
  
  
  CONCLUSIONS
  A6 demonstrated antiangiogenic properties in a rat model of CNV and may be useful in the treatment of CNV.
authors.affiliation: Joan and Irwin Jacobs Retina Center, Department of Ophthalmology, Shiley Eye Center, University of California, San Diego, La Jolla, California, USA.
authors.forename: Hyoung J
authors.initials: HJ
authors.lastname: Koh
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Bessho
authors.forename: Lingyun
authors.initials: L
authors.lastname: Cheng
authors.forename: Dirk-Uwe
authors.initials: DU
authors.lastname: Bartsch
authors.forename: Terence R
authors.initials: TR
authors.lastname: Jones
authors.forename: Germain
authors.initials: G
authors.lastname: Bergeron-Lynn
authors.forename: William R
authors.initials: WR
authors.lastname: Freeman
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005451:Fluorescein Angiography; D007208:Indocyanine Green; D007279:Injections, Subcutaneous; D017075:Laser Coagulation; D010446:Peptide Fragments / Q000627:therapeutic use*; D010960:Plasminogen Activators / Q000627:therapeutic use*; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000601:surgery; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D010446:Peptide Fragments; D005169:Factor VIII; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D007208:Indocyanine Green