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Masayuki Ashikari, Mayumi Tokoro, Masahiro Itaya, Miho Nozaki, Yuichiro Ogura; Suppression of Laser-Induced Choroidal Neovascularization by Nontargeted siRNA. Invest. Ophthalmol. Vis. Sci. 2010;51(7):3820-3824. doi: 10.1167/iovs.09-5121.
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To investigate the effect of nontargeted siRNAs on vascular leakage and vascular endothelial growth factor (VEGF)-A expression in the development of choroidal neovascularization (CNV).
Nontargeted siRNAs were 21-nt (nucleotides) siRNA-Luc (Luciferase) or 16-nt siRNA-Luc. Targeted 21-nt siRNA-Vegfa or phosphate-buffered saline (PBS) was used for comparison. Laser photocoagulation was used to induce CNV in wild-type C57BL/6J mice; 7 days later, vascular leakage was determined by fluorescein angiography, and CNV volumes were measured by confocal microscopy. Expression of VEGF-A in the retinal pigment epithelium (RPE)/choroid was quantified by ELISA 3 days after photocoagulation.
Pathologically significant leakage developed in most of the 16nt-siRNA-Luc– or PBS-injected mice but in significantly fewer 21nt-siRNA-Luc– and 21nt-siRNA-Vegfa–injected mice (P = 0.0004, P = 0.0001, respectively). CNV volume in 21-nt siRNA-Luc– and 21nt-siRNA-Vegfa–injected eyes was significantly lower than in PBS-injected eyes (P = 0.0124, P = 0.0040, respectively). CNV volume was not suppressed by 16-nt siRNA-Luc injection (P = 0.7700). The mean VEGF protein level decreased significantly in the 21nt-siRNA-Luc– and 21nt-siRNA-Vegfa–injected eyes compared with PBS-injected eyes 3 days after laser photocoagulation (P = 0.0011, P = 0.0063, respectively). The 16nt-siRNA-Luc–injected eyes did not show VEGF-A suppression 3 days after laser photocoagulation (P = 0.3177). Between 21-nt siRNA-Luc– and 21nt-siRNA-Vegfa–injected eyes, there were no significant differences in CNV volume, the VEGF-A level, or pathologic leakage detected by fluorescein.
These data suggest that nontarget 21nt-siRNA can suppress laser-induced choroidal neovascularization anatomically and functionally through VEGF suppression.
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