Abstract
Purpose::
Statins have emerged as the leading therapeutic option for the management of hypercholesterolemia associated with coronary atherosclerosis. Beyond their efficacy in reducing cholesterol, statins are now recognized as having additional significant therapeutic properties including neuroprotection. Here, we determined the effects of simvastatin pretreatment on retinal function in an ischemic animal model of glaucoma.
Methods::
Adult male Lewis rats (n=3 per group) were pretreated for three days with vehicle or simvastatin (20 mg/kg, ip). Pretreated rats were anesthetized, the anterior chamber cannulated, and the intraocular pressure was raised beyond 70 mm Hg (resting pressure 8 mm Hg) for a duration of 60 minutes followed by one week of reperfusion. Retinal function was quantitated by recording scotopic ERGs in dark-adapted pretreated rats before and one-week following ischemic insult. Body temperature was maintained at 37oC.
Results::
Scotopic ERGs recorded from the eyes of vehicle- or statin-pretreated rats prior to ischemic injury were not significantly different and exhibited a- and b-wave amplitudes (µV) of 439 ± 30 and 1237 ±76, respectively. Ischemic-reperfusion injury significantly (p<0.001) diminished ERG a- and b-wave amplitudes (µV) of vehicle-pretreated rats (148 ± 25 and 202 ± 94, respectively). In marked contrast, ERG a- and b-wave responses from simvastatin-pretreated rats were not significantly affected by the ischemic-reperfusion insult (415 ± 84 and 892 ± 221, respectively).
Conclusions::
Intraocular ischemic-reperfusion insult elicits marked deficits in retinal function as quantitated by scotopic ERG. Prophylactic administration of simvastatin protects against ischemic-reperfusion dependent deficits in retinal function. These preliminary findings suggest that statins may have therapeutic value in the early treatment of glaucoma.
Keywords: electroretinography: non-clinical • ischemia • retina