Functional and Structural Evaluation of Sildenafil in a Rat Model of Acute Retinal Ischemia/Reperfusion Injury

Abstract

Purpose: Retinal ischemia is a common cause of visual impairment and blindness. Sildenafil, a PDE5 inhibitor which inhibits cGMP degradation and in turn prolongs the effect of nitric oxide, has been shown to be protective in a number of ischemia/reperfusion (I/R) injuries, as well as in neuronal damage. We hypothesized that treatment with sildenafil might be neuroprotective in a model of acute retinal I/R injury.

Methods: Anterior chamber cannulation was performed to induce unilateral I/R injury in 38 Lewis rats. Animals received intraperitoneal injections of sildenafil (0.5 and 1 mg/kg once a day, for a period of 7 and 18 days, respectively), or saline. Electroretinography recordings, retinal ganglion cell (RGC) counts following retrograde labeling with fluorogold, histopathology, and immunohistochemistry (IHC) using antibodies against PDE5, NOS2, caspase-3, caspase-9, and Bcl-2 were conducted.

Results: No significant differences in electroretinography, RGC counts, or retinal morphometry were observed between experimental eyes of sildenafil- and saline-treated animals. A tendency toward less necrosis in histopathology, and a slight trend toward lower PDE5, NOS2, and caspase-9 and higher Bcl-2 IHC scores were evident in experimental retinas of sildenafil-treated animals.

Conclusions: Electroretinography, RGC counts, and retinal morphometry failed to show any neuroprotective effect of sildenafil in acute retinal I/R injury in rats. A slight positive effect of sildenafil was qualitatively indicated by histopathology and IHC.

Keywords: ERG; Electroretinography; I/R; IOP; retinal ganglion cells.