TY - GEN
T1 - Safety and pharmacokinetics of simvastatin using intravitreal delivery routes in the mouse retina
AU - Chung, Inyoung
AU - Tse, Yan Yin
AU - He, Feng
AU - Wensel, Theodore G.
AU - Park, Jong Moon
AU - Wu, Samuel M.
PY - 2012/3
Y1 - 2012/3
N2 - 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. 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. 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. 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.
AB - 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. 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. 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. 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.
M3 - Conference article published in proceeding or book
SN - 1552-5783
VL - 53
SP - 5391
EP - 5391
BT - Investigative Ophthalmology & Visual Science
ER -