March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Selective Blocking of APE1/Ref-1 Redox Function by a Novel Compound, APX3330 Inhibits Choroidal Endothelial Cells in vitro and Choroidal Neovascularization in vivo
Author Affiliations & Notes
  • Xiaoxi Qiao
    Ophthalmology, Henry Ford Health System, Detroit, Michigan
  • Yue Li
    Ophthalmology, Henry Ford Health System, Detroit, Michigan
  • Tongrong Zhou
    Ophthalmology, Henry Ford Health System, Detroit, Michigan
  • Xiuli Liu
    Ophthalmology, Henry Ford Health System, Detroit, Michigan
  • Mark R. Kelley
    Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
  • Paul Edwards
    Ophthalmology, Henry Ford Health System, Detroit, Michigan
  • Hua Gao
    Ophthalmology, Henry Ford Health System, Detroit, Michigan
  • Footnotes
    Commercial Relationships  Xiaoxi Qiao, None; Yue Li, None; Tongrong Zhou, None; Xiuli Liu, None; Mark R. Kelley, None; Paul Edwards, None; Hua Gao, None
  • Footnotes
    Support  NIH National Eye Institute EY019784, International Retinal Research Foundation, Midwest Eye Bank, Fund for Henry Ford Hospital.
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5559. doi:
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      Xiaoxi Qiao, Yue Li, Tongrong Zhou, Xiuli Liu, Mark R. Kelley, Paul Edwards, Hua Gao; Selective Blocking of APE1/Ref-1 Redox Function by a Novel Compound, APX3330 Inhibits Choroidal Endothelial Cells in vitro and Choroidal Neovascularization in vivo. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5559.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : We have previously demonstrated that APE1/Ref-1 redox function is required for retinal angiogenesis in vitro and in vivo. In this study, we examined the effect of APE1/Ref-1 redox inhibition by a small molecule inhibitor APX3330 on choroidal neovascularization and its potential mechanisms.

Methods: : Choroid endothelial cells (CEC, RF/6A) from rhesus monkey were used for in vitro angiogenic assays including cell proliferation, transwell migration, and Matrigel tube formation. Cells were treated with various dosages of APX3330 in comparison and in combination with an anti-VEGF antibody Avastin. The levels of HIF-1α and NFΚB were examined by western blot analysis. . The levels of VEGF and TNFα were determined by ELISA. Laser-induced choroidal neovascularization model in adult C57BL6 mice was used to determine the treatment effect of intravitreal APX3330.

Results: : APX3330 dose-dependently inhibited the proliferation, migration, and tube formation of CECs in vitro. The inhibition effect is comparable and synergistic to Avastin. Preliminary data indicate that NFΚB signaling pathway is involved in APX3330 inhibition of APE/Ref-1 redox activity in CECs. In vivo treatment of laser-induced CNV in mice also showed that a single intravitreal injection of 1 μl 200 μM APX3330 after the laser significantly reduced the size of CNV in comparison to the vehicle control group in mice (p < 0.01). There is a significant switch of the size of CNV from big ones, over 10,000 μm2 to small CNV, under 5,000 μm2.

Conclusions: : These results show that blocking of APRE1/Ref-1 with APX3330 inhibited the growth of choroidal endothelial cells in vitro and significantly reduced CNV growth in vivo. Inhibiting the redox function of APE1/Ref-1 may offer a novel approach to control choroidal neovascularization for AMD treatment.

Keywords: age-related macular degeneration • choroid: neovascularization • neovascularization 
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