April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Anti-angiogenic Effct Of Ifn-gamma And Il-12 On Laser-induced Choroidal Neovascularization Model In Mice
Author Affiliations & Notes
  • Masayuki Ashikari
    Department of Ophthalmology, Nagoya City Univ Medical School, Nagoya, Japan
  • Miho Nozaki
    Department of Ophthalmology, Nagoya City Univ Medical School, Nagoya, Japan
  • Takeshi Mizutani
    Department of Ophthalmology, Nagoya City Univ Medical School, Nagoya, Japan
  • Yuichiro Ogura
    Department of Ophthalmology, Nagoya City Univ Medical School, Nagoya, Japan
  • Footnotes
    Commercial Relationships  Masayuki Ashikari, None; Miho Nozaki, None; Takeshi Mizutani, None; Yuichiro Ogura, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1797. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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).

Conclusions: : 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.

Keywords: choroid: neovascularization • cytokines/chemokines • microscopy: confocal/tunneling 
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