Purchase this article with an account.
Xiaohui Zhang, Hironori Uehara, Subrata K. Das, Austin Bohner, Balamurali K. Ambati; AAV2.Flt23k Intraceptor Inhibits VEGF and CNV in Mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1177.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine the efficacy and safety of long-term expression of a virus mediated intraceptor vascular endothelial growth factor (VEGF) inhibitor, AAV2.Flt23k, on murine choroidal neovascularization (CNV) induced by laser photocoagulation.
To evaluate the long-term expression of AAV2 mediated gene therapy, AAV2.AcGFP was subretinal injected 1 µl (5x108 vg) and screened by Heidelberg Spectralis at 2 weeks, 1 month, 3 months and 6 months. In an experimental model of laser induced CNV, AAV2.Flt23k, and control AAV2.AcGFP and PBS were subretinal injected one month prior to laser induction. After two weeks, CNV volume was measured. VEGF level was measured with ELISA. To evaluate safety, electroretinography (ERG) and OCT retinal thickness were assessed 6 months after subretinal injection.
The AAV2.AcGFP expression was at 2 weeks and sustained expression for at least 6 months. The mean CNV volume was significantly smaller in the AAV2.Flt23k (7.60 ± 1.15 × 104 µm3) group compared with control mice treated with AAV2.AcGFP (19.81 ± 4.10 × 104 µm3, p<0.01) or PBS (16.11 ± 4.34 × 104 µm3, p<0.05). The mean VEGF protein levels decreased significantly in the treated group (376.9 ± 69.5 pg/mg, p < 0.05) compared with the control group AAV2.AcGFP (597.5 ± 52.1 pg/mg). Retinal electrical function and structural architecture were not affected by treatment.
AAV2.Flt23k can effectively long term express and inhibit laser-induced CNV in mice through downregulation of VEGF. These findings provide a promising approach for treatment of age-related macular degeneration.
This PDF is available to Subscribers Only