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Y. Qiu, A. Woolfenden, H. Gupta, S. H. Poor, B. Jaffee; Subretinal Injection of a VEGF Blocking Antibody but Not Intravitreal Injection Suppresses Choroidal Neovasculariztion in Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1191.
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© ARVO (1962-2015); The Authors (2016-present)
Study the inhibitory effects of an anti-mouse VEGF blocking antibody on mouse CNV when administered by systemic, intravitreal (IVT) and subretinal (SR) injection.
CNV was induced in 7-9 week old C57/bl6 female mice by laser injury. After pupil dilation, the mice were anesthetized and the retina was visualized with a slit lamp microscope and a cover slip. The laser (Iridex Oculight® GLx 532nm green laser) was applied at 3 locations with a successful laser shot inducing a vaporization bubble. 7 days post laser, mice were injected i.v. with a vascular label and then euthanized. Mouse eyes were fixed in 4% paraformaldehyde, RPE-choroid-scleral complexes were isolated and then mounted on a microscope slide. Fluorescent images of each laser-induced CNV were captured using a Axiocam MR3 camera on a Axio.Image M1 microscope (Zeiss) and CNV lesion size was quantified with Axiovision software (Version 4.5 Zeiss). Inter-group differences were analyzed by one-way analysis of variance (ANOVA) with a Neuman-keuls post hoc analysis. Data was masked during image acquisition and data analysis.For efficacy studies, n=10 mice/60 CNV per group. In IVT and SR experiments, 1.5ul of VEGF antibody at a concentration of 1 or 5 mg/ml was injected immediately after laser. For systemic studies, VEGF antibody was injected intraperitoneally at 0.1, 0.3, 1, 3 and 10 mg/kg on Day 0, 2 and 4. IVT injected triamcinolone at 10mg/ml was used as a positive control for the IVT experiment
Systemic administration of the VEGF antibody dose dependently inhibited CNV with an ED50 of approximately 1 mg/kg. Subretinal injection of the VEGF antibody dose dependently inhibited CNV (60% inhibition at 5mg/ml, 20% at 1 mg/ml). Intravitreal injection of triamcinolone (78% inhibition at 10 mg/ml) but not the VEGF antibody inhibited CNV.
Antibodies may not be effective in the mouse CNV model when injected IVT but work when administered by other routes. The lack efficacy from an IVT injection may reflect the blood retinal barrier blocking access to the target tissue.
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