Duration of Antiangiogenic Effect Following Periocular Delivery of Ad.PEDF.11 in Mice with Laser-Induced Choroidal Neovascularization (CNV)

Abstract

Abstract: : Purpose: Intraocular or periocular injection of E1-, E3-, E4- deleted adenoviral vector encoding human pigment epithelium-derived factor (Ad.PEDF.11) at the time of laser-induced rupture of Bruch’s membrane, suppresses the development of CNV. The aim of this study was to determine the duration of antiangiogenic effect after periocular injection of Ad.PEDF.11. Methods: Thirty-six C57Bl6 mice received periocular injection of 5x10⁹ particles of AdPEDF.11 in the right eye and no injection in the left eye. At weeks 1, 2 and 4 following vector injection Bruch’s membrane was ruptured with laser in 3 locations. Two weeks after laser treatment, mice were perfused with fluorescein- labeled dextran, choroidal flat mounts were dissected, and the area of CNV was measured at Bruch’s membrane rupture sites. CNV area was compared between treated and control eyes at each time point using a paired t-test assuming equal variance with alpha assigned a value of 0.05. Results: Eyes treated with laser, 1 week or 2 weeks after periocular injection of Ad.PEDF.11, showed significantly smaller areas of CNV at Bruch’s membrane rupture sites compared to untreated fellow eyes. At 1 week: (0.021 mm² vs. 0.032 mm², p=0.028), at 2 weeks: (0.02 mm² vs. 0.031 mm², p=0.017). When Bruch’s membrane was ruptured 4 weeks after injection of Ad.PEDF.11, there was no significant difference between treated and untreated eyes: (0.032 mm² vs. 0.047 mm², p=0.27). Conclusions: These data indicate that the antiangiogenic effect conferred by periocular injection of 5x10⁹ particles of Ad.PEDF.11 is sufficient between 2 and 4 weeks after injection to significantly suppress development of CNV.

Keywords: gene transfer/gene therapy • adenovirus • choroid: neovascularization