Sildenafil Acutely Decreases Visual Responses in ON and OFF Retinal Ganglion Cells.

Abstract

Sildenafil (Viagra), a cGMP-specific phosphodiesterase type 5 inhibitor, is widely used for the treatment of erectile dysfunction and pulmonary hypertension. Clinical studies have reported transient visual impairments in patients after single-dose sildenafil use, suggesting neural involvement in several retinal layers, and also, possibly, retinal ganglion cells (RGCs), which provide the unique output of visual information to the brain. However, the effect of sildenafil on the RGC light responses is poorly understood. We therefore evaluated its effect on RGC spiking activity. We measured spontaneous and light-induced RGC spiking activity in Long-Evans rat ex vivo retinas by using the multielectrode array technique. Sildenafil citrate (0.3-30 μM) was applied to retinal preparations under continuous perfusion, during 10 to 60 minutes, followed by sildenafil washout. A high concentration (30 μM) of sildenafil decreased the magnitudes of both ON- and OFF-type RGC light responses, to 26.3% ± 17% and 18.3% ± 7%, respectively, of the initial value, in a reversible and concentration-dependent fashion, while in 50% of RGCs all light responses were completely suppressed. Sildenafil also greatly increased the latency of both types of light responses. In this study, we provided evidence that extended exposure to both sildenafil and repeated light stimulation potentiates drug effects and delays recovery. We found transient and concentration-dependent alterations of light responses at the RGC level after sildenafil exposure that are relevant for a better understanding of the acute visual effects of administration of this compound in humans.