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Xiaohui Zhang, Hironori Uehara, Lara S Carroll, Bonnie Archer, Balamurali K Ambati; Efficacy and Safety of AAV2.Flt23k Intraceptor Compared to AAV2.sFlt01. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1449. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Intracellular VEGF should disrupt harmful autocrine VEGF feedback loops while avoiding damage to the neurosensory retina associated with chronic global VEGF suppression. We compared the efficacy and safety of intracellular versus extracellular suppression of vascular endothelial growth factor (VEGF) on laser-induced murine model of choroidal neovascularization (CNV). Inhibition of VEGF using AAV2.Flt23k intraceptors was compared to inhibition with soluble VEGF decoy receptor, AAV2.sFlt01.
AAV2.Flt23k, AAV2.LacZ, AAV2.AcGFP, and AAV2.sFlt01 were subretinally injected in 1 µl (5x108 vg) into C57/Bl6 mice. To assess efficacy, CNV was induced by argon laser (Iridex) one month after subretinal injection. CNV volume was measured two weeks after laser injury by optical coherence tomography (OCT). To evaluate safety, endoplasmic reticulum (ER) stress, TUNEL assay, and electroretinography (ERG) were assessed 4 months after subretinal injection.
The mean CNV volume was significantly smaller in the AAV2.Flt23k (0.26 ± 0.02 × 106 µm3) group than control mice treated with AAV2.LacZ (0.97 ± 0.07 × 106 µm3, p<0.0001), PBS (1.15 ± 0.12 × 106 µm3, p<0.001), or no treatment (1.07 ± 0.07 × 106 µm3, p<0.0001), but not statistically different from AAV2.sFlt01 (0.29 ± 0.03 × 106 µm3, p>0.05). Neither AAV2.Flt23k nor AAV2.sFlt01 induced apoptosis or ER stress. ERGs of both treatments were normal. N=10 in each group. Statistical analysis was performed using one-way ANOVA.
AAV2.Flt23k showed similar efficacy and safety to AAV2.sFlt01 at two week and four month endpoints, respectively.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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