Purchase this article with an account.
Yuya Ito, Miho Nozaki, Kazuhiko Sugitani, Masayuki Ashikari, Yoshio Hirano, Yuichiro Ogura; The Efficient Delivery Of Sirna By Atelocollagen On Laser-induced Choroidal Neovascularization Model In Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1789.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The previous studies have shown that target- and sequence-independent naked siRNA suppressed angiogenesis via stimulation of Toll-Like receptor (TLR) - 3 (Kleinman et al., Nature 452:591-7, 2008). Atelocollagen is a highly purified type I collagen that is modified to have low immunogenicity and siRNA/atelocollagen complex has been reported that not elicit an interferon immune response in the mice. The purpose of this study was to determine the efficacy of atelocollagen to deliver siRNA in the laser-induced CNV model.
Non-targeted siRNA, 21-nt (nucleotides) siRNA-Luc (Luciferase) was employed. PBS or atelocollagen was used for comparison. CNV was induced by laser injury in C57BL/6J mice, and volumes measured 7 days later by confocal evaluation of Griffonia simplicifolia Isolectin B4 staining of RPE-choroid flatmounts. AteloGene® Systemic Use (KOKEN, Tokyo) was complexed with naked 21-nt siRNA-Luc before injection. Naked 21-nt siRNA-Luc, 21-nt siRNA-Luc / atelocollagen complex, atelocollagen or PBS was injected into the vitreous following injury (1ug/2ul). Leakage from the CNV was also measured by fluorescein angiography 7 days after laser treatment and the lesions were graded based on the fluorescein leakage as follows: 0 (non leaky), 1 (questionable leakage), 2 (leaky) and 3 (pathologically significant leakage) by masked retina specialists.
Pathologically significant leakage (grade-3 lesions) developed in most of the PBS, atelocollagen or 21-nt siRNA-Luc /atelocollagen complex injected mice, but in significantly fewer in naked 21-nt siRNA-Luc injected mice (p<0.001). The CNV volumes were significantly smaller in the naked 21-nt siRNA-Luc compared with PBS, atelocollagen or 21-nt siRNA-Luc /atelocollagen complex injected mice (P < 0.05).
These findings demonstrate that atelocollagen might deliver siRNA without target- and sequence-independent anti-angiogenic effect in laser-CNV model.
This PDF is available to Subscribers Only