April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
AAV2.Flt23k Intraceptor Inhibits VEGF and CNV in Mice
Author Affiliations & Notes
  • Xiaohui Zhang
    Moran Eye Center, University of Utah, Salt Lake City, UT
  • Hironori Uehara
    Moran Eye Center, University of Utah, Salt Lake City, UT
  • Subrata K. Das
    Moran Eye Center, University of Utah, Salt Lake City, UT
  • Austin Bohner
    Moran Eye Center, University of Utah, Salt Lake City, UT
  • Balamurali K. Ambati
    Moran Eye Center, University of Utah, Salt Lake City, UT
  • Footnotes
    Commercial Relationships Xiaohui Zhang, None; Hironori Uehara, None; Subrata K. Das, None; Austin Bohner, None; Balamurali K. Ambati, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1177. doi:
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      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: 412 age-related macular degeneration • 701 retinal pigment epithelium • 748 vascular endothelial growth factor  

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