May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
ATN-224.021 and ATN-427.021 Suppress Choroidal Neovascularization
Author Affiliations & Notes
  • S. Kachi
    Ophthalmology and Neuroscience, Johns Hopkins University, Baltimore, Maryland
    Department of Ophthalmology, Nagoya University, Nagoya, Japan
  • N. Umeda
    Ophthalmology and Neuroscience, Johns Hopkins University, Baltimore, Maryland
  • H. Akiyama
    Ophthalmology and Neuroscience, Johns Hopkins University, Baltimore, Maryland
  • M. Kachi
    Ophthalmology and Neuroscience, Johns Hopkins University, Baltimore, Maryland
  • S. F. Hackett
    Ophthalmology and Neuroscience, Johns Hopkins University, Baltimore, Maryland
  • A. P. Mazar
    Attenuon LLC, San Diego, California
  • P. A. Campochiaro
    Ophthalmology and Neuroscience, Johns Hopkins University, Baltimore, Maryland
  • Footnotes
    Commercial Relationships  S. Kachi, None; N. Umeda, None; H. Akiyama, None; M. Kachi, None; S.F. Hackett, None; A.P. Mazar, Attenuon LLC, E; P.A. Campochiaro, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3426. doi:https://doi.org/
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    • Get Citation

      S. Kachi, N. Umeda, H. Akiyama, M. Kachi, S. F. Hackett, A. P. Mazar, P. A. Campochiaro; ATN-224.021 and ATN-427.021 Suppress Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3426. doi: https://doi.org/.

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

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Abstract

Purpose: : ATN-224.021 (ammonium tetrathiomolybdate) and its tungstate analog, ATN-427.021 (ammonium tetrathiotungstate) are copper chelators that have several effects in vitro including inhibition of superoxide dysmutase 1, inhibition of NF-ΚB, and down-regulation of several pro-angiogenic growth factors. We investigated the effects of ATN-224.021 and ATN-427.02 in a murine model of laser-induced choroidal neovascularization (CNV).

Methods: : Five week old female C57BL/6 mice had rupture of Bruch’s membrane at 3 locations in each eye and were treated orally by gavage every morning with 50 mg/kg of ATN-224.021 (14 mice), 100 mg/kg of ATN-427.021 (10 mice) or phosphate buffered saline (PBS; 10 mice). After 2 weeks, 4 of the mice treated with ATN-224.021 were euthanized and the retinas and RPE/choroid was dissected to measure the concentration of the molybdenum. The remainder of the mice were perfused with fluorescein-labeled dextran and the area of CNV at Bruch’s membrane rupture sites was measured by image analysis.

Results: : Compared to the average area of CNV in the PBS control group (6.176 ± 0.567 mm2x10-3) the area of CNV was significantly smaller in mice treated with ATN-427.021 (3.563 ± 0.356 mm2x10-3 , p=0.002 by linear mixed model) and in mice treated with ATN-224.021 (3.083 ± 0.356 mm2x10-3, p=0.0001). In mice treated with ATN-224.021, the concentration of molybdenum in the retina was 0.3503 ± 0.0990 ng/mg protein and 12.3417 ± 2.5627 ng/mg protein in RPE/choroid and was below the level of detection in the ocular tissues of control mice.

Conclusions: : ATN-224.021 and ATN-427.021 suppress CNV. Additional work is needed to determine which of their in vitro activities are responsible for the inhibition of CNV.

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