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PL Gehlbach, S Yamamoto, AM Demetriades, EW M Ng, EJ Duh, T Deering, D McVey, WL Lisa, PA Campochiaro; Periocular Adenovirus-mediated Delivery of Pigment Epithelium-derived Factor Inhibits Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4595.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the efficacy of periocular adenoviral-mediated gene transfer of pigment epithelium-derived factor (PEDF) in the treatment of murine choroidal neovascularization (CNV). Methods: Bruch’s membrane was ruptured with laser photocoagulation at 3 locations in each eye of adult C57BL/6 mice. Immediately after laser treatment, mice were given a periocular injection of 5x109 particles of an adenoviral vector expressing PEDF driven by a CMV promoter (AdPEDF.11) in one eye and 5x109 particles of corresponding control vector (AdNull.11) in the fellow eye. After 2 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. Five days after periocular vector injections in six mice, PEDF level was measured in the serum and the retina from each eye by ELISA. Results: The mean area of CNV at Bruch’s membrane rupture sites was significantly reduced (p=0.019) in eyes given a periocular injection of AdPEDF.11 (0.01220.0017 mm2, n=32) compared to fellow eyes given a periocular injection of AdNull.11 (0.03690.0097 mm2, n=33). Human PEDF was detected in serum and the retina of both eyes. Conclusion: Periocular injection of AdPEDF.11 resulted in detectable PEDF in the serum and in the retina in each eye, but the area of CNV was significantly less in the ipsilateral versus the contralateral eye. This suggest that periocular injection of AdPEDF.11 results in both systemic and local delivery of PEDF and that the later plays an important role in the inhibition of CNV. This could represent a new treatment paradigm for the treatment of ocular neovascularization.
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