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