Abstract
Abstract: :
Purpose: PEDF is a potent antiangiogenic and neurotrophic factor; gene transfer of PEDF to cells in the eye through an intravitreal injection of the adenoviral vector AdGVPEDF.11D has been shown to inhibit choroidal and retinal neovascularization in murine disease models. The current study characterizes the effects of a single intravitreal injection of AdGVPEDF.11D on laser-induced CNV in cynomolgus monkeys. Methods: A total of six primates were used; in three primates, both eyes received laser treatment to induce CNV. One eye was injected intravitreally with AdGVPEDF.11D and the contralateral eye was injected intravitreally with saline as a control. This allowed for assessment of vector safety and CNV prevention in laser treated eyes. In three other primates, only one eye received laser treatment, but both eyes were injected intravitreally with AdGVPEDF.11D. This allowed for a safety comparison between normal eyes and laser-treated eyes. The dose level for all injections was 1x109 particle units and injections were performed immediately following laser treatment. Fluorescein angiography was performed on each eye pre-study and on Days 8, 22, and 53 for the right eyes and Days 7, 21, and 41 for the left eyes. Results: Based on fluorescein angiography, CNV was present in 3 of 3 eyes receiving laser treatment and saline. Of the 6 eyes receiving laser treatment and AdGVPEDF.11D, 4 showed inhibition of CNV and 1 showed unattenuated neovasculature as compared to the control group. All eyes receiving vector experienced significant inflammatory responses and in one eye, images were obscured. Conclusion: AdGVPEDF.11D delivered by intravitreal injection showed inhibition of CNV as compared to saline-treated eyes, but vector related inflammatory responses were significant. Gene transfer of PEDF may be a promising approach to treating neovascular eye disease and further study is under consideration.
Keywords: 346 choroid: neovascularization • 419 gene transfer/gene therapy • 307 adenovirus