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