Suppression of choroidal neovascularization by nonviral gene transfer of pigment epithelium-derived factor

Age-related macular degeneration (AMD), a leading cause of vision loss among individuals over 60, is characterized by progressive retinal degeneration in a critical area for vision, the macula, and neovascular complications. Pigment epithelium-derived factor (PEDF) has the potential to address both of these pathologic processes because it has both neuroprotective and anti-angiogenic activities. In this study, we used a polymeric nonviral gene transfer platform to express PEDF in the eyes of mice and rats. In mice, there was high expression of PEDF in the retina and eyecup two weeks after subretinal injection of poly(β-amino ester) (PBAE) nanoparticles (NPs) containing a plasmid encoding PEDF, and at 2 or 4 weeks after injection there was a significant reduction in the area of choroidal neovascularization (CNV) at Bruch's membrane rupture sites compared with eyes that had received subretinal injection of a control vector. As suprachoroidal injection is a route of vector delivery that can be done in an outpatient setting and may limit certain negative side effects associated with subretinal injection, this route of administration was also investigated for PEDF plasmid delivery. In rats, there was high expression of PEDF in the retina and eyecup 4 weeks after suprachoroidal injection of PEDF NPs, and a significant reduction in CNV area at Bruch's membrane rupture sites compared with those in eyes injected with control vector. These data suggest that ocular nonviral gene transfer of PEDF may provide a new treatment approach for AMD.