Periocular Injection of an Adenoviral Vector Expressing the Extracellular Portion of Aascular Endothelial Growth Factor Receptor-1 (Adsflt.10) Inhibits Choroidal Neovascularization (CNV)

Abstract

Abstract: : Purpose: To determine the effect of periocular injection of Adsflt.10 on CNV after laser-induced rupture of Bruch’s membrane in mice. Methods: Bruch’s membrane was ruptured with laser photocoagulation at three locations in each eye of adult C57BL/6 mice. Immediately after laser treatment, mice were given a periocular injection of 3µl containing 5x10₉ particles of Adsflt.10 in one eye and 5x10₉ particles of corresponding control vector (Adnull.10) in the fellow eye, or 5µl containing 2.33x10₁₀ particles of Adsflt.10 in one eye and 2.33x10₁₀ particles of Adnull.10 in the fellow eye. After two weeks, mice were perfused with fluorescein-labeled dextran and the area of CNV at each rupture site was measured on choroidal flat mounts by computerized image analysis. Results: Compared to fellow eyes that received periocular injection of 5x10₉ particles of Ad.null.10 (CNV area = 0.03740.0106 mm₂, n=21), the mean area of CNV at Bruch’s membrane rupture sites was significantly reduced in eyes given a periocular injection of 5x10₉ particles (n=32; CNV area = 0.00980.0017 mm₂; p=0.015) or 2.33x10₁₀ particles of Adsflt.10 (n=21; CNV area = 0.0087 0.0024 mm₂, p=0.013). The difference between low and high dose Adsflt.10 was not significant (p=0.728). Conclusion: Periocular injection of Adsflt.10 inhibits CNV in the ipsilateral, but not the contralateral eye implicating local delivery of sflt in the inhibitory effect.

Keywords: 419 gene transfer/gene therapy • 346 choroid: neovascularization • 307 adenovirus