Antiangiogenic effect of oral 2-methoxyestradiol on choroidal neovascularization in mice.
We evaluated the efficacy of systemic 2-methoxyestradiol (2ME2) in a laser-induced murine model of choroidal neovascularization (CNV). C57BL/6J mice (8-week-old males) were used in this study and divided into four groups. After laser treatment, daily oral treatment with vehicle control, and 30, 50, and 75 mg/kg of 2ME2 was started. Two weeks after laser treatment, digital images of CNV were obtained from fluorescein isothiocyanate-dextran (FITC-dextran) angiography and choroidal flat mount after FITC-dextran perfusion. These images were quantified by NIH image software. Analysis of images from both FITC-dextran angiography and choroidal flat mount with FITC-dextran perfusion demonstrated that the 2ME2 treated groups showed a statistically significant, dose-dependent decrease in CNV. No toxicity or weight loss was observed during the treatment. Significant antiangiogenic effects of oral 2ME2 on laser induced CNV were observed. Since 2ME2 (Panzem) has demonstrated good safety in phase I/II trials for cancer, it has the potential to be used as a novel oral treatment for age-related macular degeneration.
Funakoshi
Taisaku
T
Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Karp 11.210, Boston, MA 02115, USA.
Birsner
Amy E
AE
D'Amato
Robert J
RJ
D000077584:2-Methoxyestradiol; D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D002829:Choroid / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005451:Fluorescein Angiography / Q000379:methods; D007091:Image Processing, Computer-Assisted / Q000379:methods; D017075:Laser Coagulation / Q000379:methods; D008268:Macular Degeneration / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D020533:Angiogenesis Inhibitors; D004958:Estradiol; D000077584:2-Methoxyestradiol