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Yoshio Hirano, Hiroki Kaneko, Judit Baffi, Sami Dridi, Valeria Tarallo, Sasha Bogdanovich, Bradley Gelfand, Mark E. Kleinman, Royce Mohan, Jayakrishna Ambati; Genetic Confirmation Of Target-independent Suppression Of Choroidal Neovascularization By siRNAs Via TLR3. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1766.
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We previously reported that non-targeting, cell-impermeant siRNAs can suppress neovascularization in various models of angiogenesis via generic activation of toll-like receptor 3 (TLR3) without triggering RNA interference. In this study, we examined whether siRNAs targeting Vimentin or Timp2 could suppress laser-induced choroidal neovascularization (CNV) in Vim-/-, Timp2-/-, and Tlr3-/- mice.
The CNV responses of Vim-/-, Timp2-/-, and Tlr3-/- mice treated with intravitreous administration of siRNA-Vimentin or siRNA-Timp2 were quantified by volumetric analysis.
siRNA-Vimentin and siRNA-Timp2 suppressed CNV in mice deficient in these genes, respectively. However, CNV was not suppressed by these siRNAs in Tlr3-/- mice.
These results provide genetic corroboration of target-independent suppression of CNV by siRNAs via TLR3.
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