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Yang Liu, zida li, Dan reef, Jingtai Cao, Carl Romano, Stanley J Wiegand; Systemic Administration of Anti-Angiopoietin-2 (Ang-2) Antibody Inhibits Matrigel Induced Choroidal Neovascularization (CNV) in Rats . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2359.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the inhibitory effects of REGN910-mediated pharmacological inhibition of Ang-2 on CNV using a rat model of choroidal neovascularization (CNV).
CNV was induced in Sprague Dawley (SD) rats by a subretinal injection of Matrigel on Day 0. One group of animals (animals: N=4-6; eyes: N=8-12) was used to establish a baseline and animals were perfused with a dye [1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindocarbocyanine Perchlorate (DiI)] to stain vessels 10 days after CNV induction. The other animals were divided into two groups (animals: N=5-6, and eyes: N=10-12, in each group) and treated with masked solutions by subcutaneous injection of 25 mg/kg REGN910, or 6.5 mg/kg hFc at equimolar amount relative to REGN910, respectively, on days 10, 13, and 16 followed by perfusion with DiI to stain vessels on Day 20. Subretinal lesion and CNV vessel volumes were quantified from 50 µm sections throughout the entire lesion. The results from two identical experiments were combined for lesion volume, vessel volume, and vessel density comparison among three groups. A two-tailed Student t-test was used to compare the differences of lesion volume, vessel volume, and vessel density between groups treated with REGN910 versus hFc.
Systemic administration of REGN910 (25 mg/kg) to SD rats produced a suppression of the total lesion volume and vessel volume compared to hFc-treated control. In the hFc treated group, subretinal lesion volume, neovessel volume, and neovessel density increased by 28.2%, 62.5%, and 28.6%, respectively, by Day 20, relative to the baseline at Day 10. The REGN910 treated group showed 26.5% reduction of total lesion volume, and 26.9% reduction of vessel volume, compared to hFc treated group, though the vessel density was unchanged compared to the hFc treated group. Compared to hFc-treated controls, the REGN910 treated group showed statistically significant reduction of total lesion volume (p=0.0034), and a trend (26.9%) towards neovessel volume reduction, but this trend did not achieve statistical significance (p=0.1658, which may have been due to variation within the group).
The results indicate that systemic (subcutaneous) treatment with REGN910 can significantly inhibit Matrigel induced CNV lesion in rats.
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