Intravitreal AAV-IKV mediated delivery of decorin inhibits choroidal neovascularization, fibrosis, inflammation and elevates autophagy

Abstract

Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly. The exudative or wet form of AMD is caused by choroidal neovascularization (CNV) and subsequently a macular edema. Wet AMD can be effectively treated with anti-vascular endothelial growth factor (VEGF) therapies. However, despite treatment, more than half of patients continue to lose vision due to a lack of compliance with frequent intravitreal injections, failure to adequately respond to anti-VEGF therapy and emergence of fibrotic scars underneath the retina. In this study we investigated the use of our retinal penetrating AAV for delivery of human decorin (AAV-IKV-Decorin) in a murine model of laser induced CNV. Our results indicate that following a single intravitreal injection, decorin is highly expressed in the outer retina of AAV-IKV-Decorin injected mice and such mice exhibit significantly less neovascularization in laser induced CNV relative to mice injected with an AAV-IKV-Aflibercept, an AAV expressing an anti-VEGF. AAV-IKV-Decorin also significantly inhibited fibrosis, reduced inflammatory markers and increased autophagy.