Anti-angiogenic effects of non-peptide integrin alphavbeta3 specific antagonist on laser-induced choroidal neovascularization in mice.
BACKGROUND
To evaluate the anti-angiogenic effects of integrin alphavbeta3 specific antagonist BS-1417 on laser-induced choroidal neovascularization (CNV) in mice.


METHODS
Male C57BL/6 mice were treated with daily intraperitoneal injections of BS-1417 or saline starting at the onset (day 0) of experiments. CNV was induced by laser photocoagulation the next day. Fluorescein angiograms (FA) and choroidal flatmount FITC-dextran perfusion were performed on experimental day 8. Histological and immunohistochemical examinations were performed with consecutive cryosections. Sub-confluent human vascular endothelial cells (HUVEC) were grown in vitro under various concentrations (0-10 microg/ml) of BS-1417 and the numbers of cell were measured at 48 hours of incubation. After fixation, immunocytochemistry was performed.


RESULTS
BS-1417 significantly decreased the area of dye leakage determined by FA (40% of control, p = 0.0008) and reduced the CNV size found on choroidal flatmount (18% of control, p = 0.007). In histological findings, BS-1417 apparently suppressed the size of laser-induced CNV. Immunoreactivities for VEGF and integrin alphav were remarkably attenuated with BS-1417 compared to control. BS-1417 inhibited the growth and VEGF expression of HUVEC in vitro.


CONCLUSIONS
The integrin alphavbeta3 may play a key role in the induction of laser-induced CNV. The antagonists for integrin alphavbeta3 may have therapeutic effects in CNV associated diseases such as age-related macular degenerations.
Honda
Shigeru
S
Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine,Chuo-ku, Kobe 650-0017, Japan. sighonda@med.kobe-u.ac.jp
Nagai
Takayuki
T
Negi
Akira
A
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002452:Cell Count; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005451:Fluorescein Angiography; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D017075:Laser Coagulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; C539746:BS 1417; D039302:Integrin alphaVbeta3; D010879:Piperazines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A