title: Anti-angiogenic effect of KR-31831 on corneal and choroidal neovascularization in rat models.
abstract: OBJECTIVE
  We attempt to determine the effect and mechanism of KR-31831 in rat models of corneal neovascularization and choroidal neovascularization (CNV).
  
  
  METHODS
  Corneal neovascularization was induced by silver nitrate cauterization. Balanced salt solution (for control), KR-31831 (0.1 mg/mL), and bevacizumab (10 mg/mL) were applied topically with or without subsequent subconjunctival injection (10 μL). The degree of corneal neovascularization was compared among treatments. The effects of intravitreal (0.1 and 0.3 mg/mL) and intraperitoneal (25 mg/kg) of KR-31831, and intravitreal injection of bevacizumab (2.5 mg/mL) were compared in a laser-induced CNV model. FITC-dextran was used to observe the choroid vessels and to evaluate vessel leakage by fluorescence intensity.
  
  
  RESULTS
  In the silver nitrate cauterized rat, topical KR-31831 (P = 0.008) or bevacizumab (P = 0.008) reduced effectively the area of corneal neovascularization compared to control on day 14. This was reduced further by additional subconjunctival injection of KR-31831 (P = 0.024) and bevacizumab (P = 0.016). After KR-31831 application, vascular endothelial growth factor (VEGF) receptor 2 and matrix metalloproteinase (MMP)-2 expression was decreased in the cornea. In the CNV model, intravitreal (0.3 mg/mL) and intraperitoneal KR-31831 inhibited significantly the CNV area (P = 0.008 and P = 0.008, respectively) and fluorescence leakage (P = 0.008 and P = 0.032, respectively). This effect was more significant compared to intravitreal bevacizumab in terms of the CNV area (P = 0.032 and P = 0.008, respectively) and fluorescence leakage (P = 0.016 and P = 0.008, respectively).
  
  
  CONCLUSIONS
  The anti-angiogenic effect of KR-31831 was comparable in the cornea and more effective in the choroid compared to that of bevacizumab, and it may exert its effect by VEGF signaling and MMP-2.
authors.affiliation: Kim and Kim Eye Clinic, Seoul, Korea.
authors.forename: In-Tae
authors.initials: IT
authors.lastname: Kim
authors.forename: Hae-Young Lopilly
authors.initials: HY
authors.lastname: Park
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Choi
authors.forename: Choun-Ki
authors.initials: CK
authors.lastname: Joo
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005136:Eye Proteins / Q000378:metabolism; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism
chemical_list: D001578:Benzopyrans; D005136:Eye Proteins; D007093:Imidazoles; C503693:KR 31831; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2