Fig. 5. Effect of suprachoroidal or subretinal injection of NPs containing a VEGF-neutralizing protein expression plasmid.
There was a significant increase in sFlt1 retinal protein 1 month after suprachoroidal injection of PBAE NPs containing 1 μg of p3sFlt1Fc (A) (n = 5; *P = 0.043 by Wilcoxon signed-rank test). Two weeks after suprachoroidal injection of 1 μg of p3sFlt1Fc in NPs (one eye) and 1 μg of pCMV-Luc in NP (other eye), 100 ng of VEGF165 was injected into both eyes. After 12 hours, Evans Blue assay showed significantly less dye leakage in p3sFlt1Fc-injected eyes (B) (n = 7; *P = 0.011 by paired t test). At P14, rho/VEGF mice were given subretinal injection of 1 μg of p3sFlt1Fc in NP (one eye) and 1 μg of pCMV-Luc in NP (other eye). At P35 (n = 8), RPE/choroid flat mounts stained with DyLight 594–labeled GSA showed red dots throughout control flat mounts (C) seen to be subretinal neovascularization (NV) by magnification (C) (upper right), which was decreased in sFlt1 NP-injected eyes (D) (magnified box, lower left). The mean area of NV per flat mount was significantly less in the p3sFlt1Fc NP group (E) (*P = 0.025 by Wilcoxon signed-rank test). This difference was maintained at P70 (F to H) (n = 6; *P = 0.046 by Wilcoxon signed-rank test).