title: Comparative study of tacrolimus and bevacizumab on corneal neovascularization in rabbits.
abstract: OBJECTIVE
  To compare the antiangiogenic effects of tacrolimus and bevacizumab on corneal neovascularization (CNV) in rabbits.
  
  
  METHODS
  Neovascularization was induced in 32 eyes of 16 rabbits by placing a suture in the corneal stroma. Seven days after suture placement, all rabbits were divided into 4 groups and were treated subconjunctivally with bevacizumab (AVA_sub) 0.05 mL (5 mg/0.05 mL), tacrolimus (TAC_sub) 0.05 mL (0.25 mg/0.05 mL), balanced salt solution (0.05 mL was subconjunctivally injected in 1 eye of each rabbit and applied by eye drops in the other eyes, control group), and tacrolimus eye drops (TAC_drop) (5 mg/5 mL applied 4 times daily). Digital photographs were obtained and surface area of CNV was measured 7 days after subconjunctival injections. Corneal specimens were analyzed histopathologically and were used to measure the concentration of vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-1 beta (IL-1β), and monocyte chemoattractant protein 1 mRNA by reverse transcription polymerase chain reaction.
  
  
  RESULTS
  In digital photographs, the neovascularized area was decreased in all treatment groups (AVA_sub, 0.58; TAC_sub, 0.60; TAC_drop, 0.68) compared with the control group (balanced salt solution, 0.81). Histological examination showed markedly regressed new vessels in treatment groups, and immunohistochemical staining revealed weakly stained anti-VEGF and anti-F4/80 antibodies in treatment groups. In semiquantitative reverse transcription polymerase chain reaction, concentration of VEGF (AVA_sub, 0.24; TAC_drop, 0.18), TNF-α (AVA_sub, 0.19; TAC_sub, 0.24; TAC_drop 0.15), and IL-1β (AVA_sub, 0.19; TAC_sub, 0.33; TAC_drop, 0.18) mRNA were significantly lower in treatment groups than in the control group (VEGF, 0.47; TNF-α, 0.44; IL-1β, 0.87) (P < 0.05).
  
  
  CONCLUSIONS
  Topical and subconjunctival tacrolimus application may be useful in reducing CNV and have comparable effects to subconjunctival bevacizumab injection.
authors: Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors: Jin-Heung
authors: JH
authors: Park
authors: Choun-Ki
authors: CK
authors: Joo
authors: Sung Kun
authors: SK
authors: Chung
mesh_terms: D000287:Administration, Topical; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D018932:Chemokine CCL2 / Q000235:genetics; D003228:Conjunctiva / Q000187:drug effects; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D056965:Injections, Intraocular; D007371:Interferon-gamma / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D009883:Ophthalmic Solutions; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D016559:Tacrolimus / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018932:Chemokine CCL2; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D009883:Ophthalmic Solutions; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D007371:Interferon-gamma; D016559:Tacrolimus