Abstract
Purpose: :
The objective of this study is to determine retinal toxicity and pharmacokinetic profile after intravitreal injection of Simvastatin in mice. Simvastatin is a potent statins that has been shown to protect retinal ganglion cells (RGCs) from degenerative insults. Our long-term goal is to investigate the neuroprotective actions of Simvastatin on RGCs in chronic and acute glaucoma mouse models.
Methods: :
Simvastatin (1ul of 500uM) was injected into the vitreous of the right eye of the mice, and the vehicle solution was injected into the left eye as a control. Simultaneous bilateral dark-adapted electroretinography (ERG) was performed 1, 3 and 7 days following the injection. High-performance liquid chromatography (HPLC) of the isolated mouse retina was used to determine drug concentrations at 6, 24, 48 hours after injection.
Results: :
The amplitude and kinetics of the ERG a- and b-wave exhibited no statistically significant differences between the two eyes in the all mice tested. Average retinal levels of Simvastatin (determined by HPLC) was 2.33 pmol (or 0.96 ng)/retina 6hrs after intravitreal injection, 9.55 pmol (3.99 ng)/retina 24 hrs, and 10.05 pmo(4.2ng)/retina 48 hrs after injection.
Conclusions: :
Intravitreal injection of 500uM Simvastatin is safe in the mice, as the retinas show no sign of dysfunction days after injection (no change in ERG a- and b-wave). Simvastatin levels in the retina maintains for at least 48 hours, suggesting intravitreal injection is a reasonable way to deliver this neuroprotective agent for potential therapeutic treatment of retinal diseases such as glaucoma.
Keywords: drug toxicity/drug effects • electroretinography: non-clinical • retina