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Updated: Jul 9, 2026
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
Antiangiogenic effects of bisphosphonates on laser-induced choroidal neovascularization in mice
Takayuki Nagai1, Hisanori Imai, Shigeru Honda
1Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan.
Purpose:
To demonstrate that bisphosphonates inhibit laser-induced choroidal neovascularization (CNV) in vivo and downregulate angiogenic gene expression in retinal pigment epithelial cells in vitro.
Methods:
Male C57BL/6 mice were treated with intraperitoneal injections of alendronate, clodronate, or saline at the onset (day 0) of experiments. CNV was induced by laser photocoagulation the next day, and fluorescein angiography (FA) was performed on experimental days 7 and 14. Histologic and immunohistochemical examinations were performed on day 7. ARPE-19 cells were grown on multi-plate wells coated with type I collagen to induce the gene expression of VEGF and integrins. Alendronate or clodronate was applied for 3 days, and real-time PCR was performed to measure VEGF-A, VEGF-B, and VEGF-C and integrin-alphaV, integrin-beta1, and integrin-beta3.
Results:
Alendronate and clodronate significantly suppressed the size of laser-induced CNV. Immunoreactivities for VEGF and integrin-alphaV were remarkably attenuated with alendronate and mildly reduced with clodronate. Alendronate significantly downregulated the gene expression profiles of VEGF and integrins, whereas clodronate had no effect in ARPE-19 cells.
Conclusions:
Although only adverse effects of bisphosphonate have been documented in the ophthalmologic literature, some therapeutic effects of bisphosphonates, including antiangiogenesis, may be expected in ocular diseases. Antiangiogenic mechanisms of bisphosphonates may vary; further investigation is needed.
Insights
Bisphosphonates, like alendronate, show potential in treating eye diseases by inhibiting choroidal neovascularization (CNV). These drugs may also reduce the expression of genes linked to blood vessel growth.
Area of Science:
- Ophthalmology
- Pharmacology
- Molecular Biology
Background:
- Choroidal neovascularization (CNV) is a major cause of vision loss.
- Bisphosphonates are primarily known for treating bone diseases.
- Ocular adverse effects of bisphosphonates are documented, but therapeutic potential is less explored.
Purpose of the Study:
- To investigate the anti-angiogenic effects of bisphosphonates in laser-induced CNV in vivo.
- To determine if bisphosphonates downregulate angiogenic gene expression in retinal pigment epithelial cells in vitro.
Main Methods:
- Bisphosphonates (alendronate, clodronate) or saline were administered to mice.
- CNV was induced via laser photocoagulation, followed by fluorescein angiography and histological analysis.
- ARPE-19 cells were treated with bisphosphonates to assess gene expression of VEGF and integrins using real-time PCR.
Main Results:
- Alendronate and clodronate significantly reduced the size of CNV lesions in mice.
- Alendronate markedly decreased VEGF and integrin-alphaV immunoreactivity.
- Alendronate significantly downregulated VEGF and integrin gene expression in ARPE-19 cells, while clodronate had no effect.
Conclusions:
- Bisphosphonates demonstrate anti-angiogenic properties relevant to ocular diseases.
- The therapeutic potential of bisphosphonates in ophthalmology warrants further investigation.
- Mechanisms underlying the anti-angiogenic effects of bisphosphonates may differ and require more study.
