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Updated: May 7, 2026
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
Efficient delivery of siRNA by atelocollagen in a murine laser-induced choroidal neovascularization model
Yuya Ito1, Miho Nozaki, Kazuhiko Sugitani
1Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
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.
Insights
Atelocollagen effectively delivered small interfering RNA (siRNA) to reduce choroidal neovascularization (CNV) in mice. This method avoids nonspecific toll-like receptor-3 (TLR3) stimulation, offering a promising approach for treating angiogenesis-related eye diseases.
Area of Science:
- Ophthalmology
- Molecular Biology
- Biotechnology
Background:
- Small interfering RNAs (siRNAs) can suppress angiogenesis by stimulating toll-like receptor-3 (TLR3).
- Delivery of siRNA without off-target effects is crucial for therapeutic applications.
- Choroidal neovascularization (CNV) is a significant cause of vision loss.
Purpose of the Study:
- To evaluate atelocollagen as a carrier for siRNA delivery in a laser-induced CNV mouse model.
- To determine if atelocollagen mediates siRNA delivery without stimulating TLR3.
- To assess the efficacy of siRNA-Vegfa delivered by atelocollagen in reducing CNV.
Main Methods:
- CNV was induced by laser injury in C57BL/6J mice.
- Nontargeted siRNA, siRNA-Luc, and siRNA-Vegfa were administered via intravitreal injection, with and without atelocollagen complexation.
- Chloroquine was used to block TLR3 endosomal activity.
Main Results:
- Mean CNV volumes were significantly reduced in groups receiving naked siRNA-Luc, naked siRNA-Vegfa, or siRNA-Vegfa/atelocollagen complex compared to controls (p < 0.05).
- Atelocollagen-mediated delivery of siRNA-Vegfa demonstrated efficacy in reducing CNV.
- Naked siRNA also showed efficacy, suggesting potential for non-complexed delivery.
Conclusions:
- Atelocollagen can deliver siRNA effectively in the murine laser-CNV model.
- This delivery method appears to avoid nonspecific TLR3 stimulation.
- Atelocollagen holds potential as a safe and effective siRNA carrier for treating CNV.
