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Updated: Jun 27, 2026
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
Anti-angiogenic effects of non-peptide integrin alphavbeta3 specific antagonist on laser-induced choroidal
Shigeru Honda1, Takayuki Nagai, Akira Negi
1Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine,Chuo-ku, Kobe 650-0017, Japan. sighonda@med.kobe-u.ac.jp
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.
Insights
The integrin alphavbeta3 antagonist BS-1417 effectively reduced choroidal neovascularization (CNV) in mice by inhibiting vascular endothelial growth factor (VEGF) and cell proliferation. This suggests potential therapeutic applications for CNV-associated eye diseases.
Area of Science:
- Ophthalmology
- Angiogenesis Research
- Pharmacology
Background:
- Choroidal neovascularization (CNV) is a key pathology in age-related macular degeneration.
- Integrin alphavbeta3 is implicated in the development of CNV.
- Targeting integrin alphavbeta3 offers a potential therapeutic strategy for CNV.
Purpose of the Study:
- To evaluate the anti-angiogenic effects of the integrin alphavbeta3 specific antagonist BS-1417.
- To assess the efficacy of BS-1417 in a laser-induced mouse model of CNV.
- To investigate the impact of BS-1417 on vascular endothelial cell growth and VEGF expression in vitro.
Main Methods:
- Male C57BL/6 mice received daily intraperitoneal injections of BS-1417 or saline.
- CNV was induced via laser photocoagulation.
- Angiography, choroidal flatmounts, histology, and immunohistochemistry were performed.
- Human umbilical vein endothelial cells (HUVEC) were cultured with BS-1417 to assess cell growth and VEGF expression.
Main Results:
- BS-1417 significantly reduced dye leakage (40% reduction) and CNV size (82% reduction) in laser-induced CNV.
- Histological analysis confirmed suppressed CNV lesion size.
- BS-1417 treatment attenuated immunoreactivity for VEGF and integrin alphav.
- In vitro, BS-1417 inhibited HUVEC growth and VEGF expression.
Conclusions:
- Integrin alphavbeta3 plays a critical role in laser-induced CNV.
- Integrin alphavbeta3 antagonists, like BS-1417, demonstrate therapeutic potential for CNV.
- These findings support the development of BS-1417 for treating CNV-related diseases, including age-related macular degeneration.
