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Masayuki Ashikari, Miho Nozaki, Takeshi Mizutani, Yuichiro Ogura; Anti-angiogenic Effct Of Ifn-gamma And Il-12 On Laser-induced Choroidal Neovascularization Model In Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1797.
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The previous studies have shown that target- and sequence-independent siRNA suppressed angiogenesis via stimulation of Toll-Like receptor (TLR) - 3 (Kleinman et al., Nature 452:591-7, 2008). In their studies, the mechanism underlying the anti-angiogenesis effect by the siRNA was thought to be involved with IFN-gamma and IL-12. The purpose of this study was to determine the effects of IFN-gamma or IL-12 in the laser-induced CNV model.
We employed recombinant mouse IFN-gamma (10ng, 100ng), recombinant mouse IL-12 (1ng, 10ng). PBS 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. IFN-gamma, IL-12 or PBS was injected into the vitreous following injury. 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.
Both IFN-gamma and IL-12 suppressed CNV in a dose-dependent manner. The mean CNV volume was significantly smaller in the IFN-gamma (100ng) (2.3± 2.5 x 105 µm3), IL-12 (10ng) (1.3 ± 1.8x 105 µm3) compared with PBS injected mice (3.7 ± 4.8x 105 µm3; p = 0.0232, p =0.0007, respectively). Pathologically significant leakage (grade-3 lesions) developed in most of the PBS injected mice, but in significantly fewer in IFN-gamma (100ng) and IL-12 (10ng) injected mice (p<0.05).
Collectively these findings demonstrate that IFN-gamma or IL-12 can suppress laser-induced CNV, and the anti-angiogenesis effect by the siRNA might be generated via IFN-gamma or IL-12, which are at downstream of TLR3 signaling pathway.
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