Efficient Delivery of siRNA by Atelocollagen in a Murine Laser-Induced Choroidal Neovascularization Model

Purpose: Previous studies have shown that small interfering RNAs (siRNAs) could suppress angiogenesis via stimulation of toll-like receptor-3 (TLR3). The purpose of this study was to determine the efficacy of atelocollagen to deliver siRNA without TLR3 stimulation in the laser-induced choroidal neovascularization (CNV) model. Methods: CNV was induced by laser injury in C57BL/6J mice and volumes were measured 7 days later. Nontargeted siRNA, 21-nucleotide (nt) siRNA-Luc (Luciferase) and 21-nt siRNA-Vegfa were injected into the vitreous following injury. Atelocollagen was incubated with naked 21-nt siRNAs before injection. To block TLR3 endosomal activity, chloroquine was injected intravitreously after laser injury. Results: The mean CNV volumes were significantly smaller in the naked siRNA-Luc, naked siRNA-Vegfa, or siRNA-Vegfa/atelocollagen complex compared with PBS, atelocollagen or siRNA-Luc/atelocollagen complex-injected mice (p < 0.05). Conclusion: These findings demonstrate that atelocollagen may deliver siRNA without nonspecific TLR3 stimulation in the murine laser-CNV model.