May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Possible Role of Methylnaltrexone (MNTX) in Retinal Angiogenesis
Author Affiliations & Notes
  • J. J. Kang Derwent
    Dept of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois
  • A. Appel
    Dept of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois
  • K. Triandafilou
    Dept of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois
  • S. Benac
    Dept of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois
  • J. Moss
    Dept. of Anesthesia and Critical Care,
    University of Chicago, Chicago, Illinois
  • W. F. Mieler
    Dept. of Ophthalmology and Visual Science,
    University of Chicago, Chicago, Illinois
  • Footnotes
    Commercial Relationships  J.J. Kang Derwent, None; A. Appel, None; K. Triandafilou, None; S. Benac, None; J. Moss, None; W.F. Mieler, None.
  • Footnotes
    Support  The Macula Foundation
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3446. doi:https://doi.org/
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    • Get Citation

      J. J. Kang Derwent, A. Appel, K. Triandafilou, S. Benac, J. Moss, W. F. Mieler; Possible Role of Methylnaltrexone (MNTX) in Retinal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3446. doi: https://doi.org/.

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

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Abstract

Purpose: : In vitro experiments have demonstrated that methylnaltrexone (MNTX), a peripheral opioid antagonist, inhibits opioid and VEGF-induced angiogenesis. The main objective is to investigate the role of MNTX in retinal angiogenesis assessed by changes in vascular and retinal cellular function.

Methods: : Dark-adapted corneal single- and paired-flash electroretinogram (ERG) responses were recorded from anesthetized pigmented adult rats. The a-wave amplitude-intensity response was obtained by varying flash intensity (0.75 to 507 sc cd s m-2). The full time course of the derived rod response was obtained for four test flash strengths (0.8, 2.6, 13 and 30 sc cd s m-2). Measurements were obtained after intravitreal injection of i) morphine alone (3 µl of 0.01 - 1 mM vit conc), ii) MNTX alone (3 µl of 0.01 - 0.1 mM vit conc) and iii) a combination of morphine (0.01 mM vit conc) and MNTX (0.01 mM vit conc) separated by 24 hours. Data were obtained at 24 hours, day 3, week 1 and week 2 after the injection. After each ERG experiment, scanning laser ophthalmoscope infrared reflectance and fluorescein angiogram images were obtained to measure changes in vasculature.

Results: : Injection of morphine caused a dose-dependent increase in vasodilation by 24 hours after the injection. The normalized amplitude-intensity relation was shifted by ~0.2 log unit by 24 hours post-injection. The time course of the morphine treated responses were slightly longer (~100 ms) than the controls. Injection of MNTX also caused a significant vasodilation by 24-hours post-injection. However, the amplitude-intensity relation and time course were similar to the controls. A combination of morphine and MNTX showed no significant vasodilation. A small ERG change occurred due to the morphine injection was reversed by the MNTX injection.

Conclusions: : The data suggest that MNTX may interact with vasoactive substances and that MNTX may be another potential agent that can be used to suppress retinal angiogenesis.

Keywords: retinal neovascularization • electroretinography: non-clinical 
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