Antiangiogenic effects of bisphosphonates on laser-induced choroidal neovascularization in mice.
ABSTRACT To demonstrate that bisphosphonates inhibit laser-induced choroidal neovascularization (CNV) in vivo and downregulate angiogenic gene expression in retinal pigment epithelial cells in vitro.
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.
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.
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.
Article: Therapeutic effect of oral bisphosphonates on choroidal neovascularization in the human eye.[show abstract] [hide abstract]
ABSTRACT: Purpose. Choroidal neovascularization (CNV) is often associated with age-related macular degeneration (AMD) and pathological myopia (PM). Bisphosphonates, the drug of choice to treat osteoporosis, have been recently reported to have anti-angiogenic effects. The purpose of this study is to investigate the therapeutic effects of oral bisphosphonates for CNV in humans. Methods. Thirty-six consecutive cases with CNV due to AMD or PM who declined anti-VEGF therapy were recruited. The patients were prescribed 5 mg of oral alendronates daily for 6 months. The best-corrected visual-acuity (BCVA), the lesion size in fundus photographs and fluorescein angiography, foveal thickness and total macular volume in optical coherence tomography were compared between pre- and post-treatment. Results. The mean BCVA of the patients was significantly improved after a months with the treatment in the AMD group. In the PM group, the mean BCVA was maintained up to 6 months with the treatment. The mean lesion size was significantly decreased by 3 months in both groups. The averages of foveal thickness and total macular volume were significantly reduced after 1 month of treatment in the AMD group.Conclusions. Oral bisphosphonate should be further investigated as a possible therapeutic and preventive drug for CNV due to AMD and PM.Journal of Ophthalmology 01/2010; 2010.