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Updated: Aug 7, 2026
An Ex Vivo Choroid Sprouting Assay of Ocular Microvascular Angiogenesis
Published on: August 6, 2020
Antiangiogenic effect of oral 2-methoxyestradiol on choroidal neovascularization in mice
Taisaku Funakoshi1, Amy E Birsner, Robert J D'Amato
1Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Karp 11.210, Boston, MA 02115, USA.
Abstract:
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.
Insights
Systemic 2-methoxyestradiol (2ME2) significantly reduced choroidal neovascularization (CNV) in mice. This antiangiogenic effect was dose-dependent and showed no toxicity, suggesting potential for treating age-related macular degeneration.
Area of Science:
- Ophthalmology
- Angiogenesis Research
- Pharmacology
Background:
- Choroidal neovascularization (CNV) is a key pathology in age-related macular degeneration (AMD).
- Current treatments for wet AMD have limitations, necessitating novel therapeutic strategies.
- 2-methoxyestradiol (2ME2) is an endogenous metabolite with known antiangiogenic properties.
Purpose of the Study:
- To evaluate the efficacy of systemically administered 2-methoxyestradiol (2ME2) in a laser-induced murine model of CNV.
- To determine the dose-dependent effects and safety profile of oral 2ME2 treatment for CNV.
Main Methods:
- A laser-induced CNV model was established in C57BL/6J mice.
- Mice received daily oral treatments of vehicle control or varying doses of 2ME2 (30, 50, 75 mg/kg).
- CNV size was quantified using fluorescein isothiocyanate-dextran (FITC-dextran) angiography and choroidal flat mounts two weeks post-treatment.
Main Results:
- 2ME2 treatment resulted in a statistically significant, dose-dependent reduction in CNV size.
- Both FITC-dextran angiography and choroidal flat mount analyses confirmed the antiangiogenic effects.
- No observable toxicity or weight loss was noted in the 2ME2 treated groups.
Conclusions:
- Systemic oral 2ME2 demonstrates significant antiangiogenic efficacy in a preclinical model of CNV.
- The favorable safety profile observed in this study, coupled with prior human trial data, supports 2ME2's potential as an oral therapy for AMD.
- 2ME2 represents a promising novel therapeutic candidate for neovascular eye diseases like AMD.
