TY - JOUR

T1 - Progressive Effects of Sildenafil on Visual Processing in Rats

AU - Østergaard, Freja Gam

AU - Wade, Alex R

AU - Siebner, Hartwig Roman

AU - Christensen, Kenneth Vielsted

AU - Laursen, Bettina

N1 - Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

PY - 2020

Y1 - 2020

N2 - Photoreceptors are light-sensitive cells in the retina converting visual stimuli into electrochemical signals. These signals are evaluated and interpreted in the visual pathway, a process referred to as visual processing. Phosphodiesterase type 5 and 6 (PDE5 and 6) are abundant enzymes in retinal vessels and notably photoreceptors where PDE6 is exclusively present. The effects of the PDE inhibitor sildenafil on the visual system, have been studied using electroretinography and a variety of clinical visual tasks. Here we evaluate effects of sildenafil administration by electrophysiological recordings of flash visual evoked potentials (VEPs) and steady-state visual evoked potentials (SSVEPs) from key regions in the rodent visual pathway. Progressive changes were investigated in female Sprague-Dawley rats at 10 timepoints from 30 min to 28 h after peroral administration of sildenafil (50 mg/kg). Sildenafil caused a significant reduction in the amplitude of VEPs in both visual cortex and superior colliculus, and a significant delay of the VEPs as demonstrated by increased latency of several VEP peaks. Also, sildenafil-treatment significantly reduced the signal-to-noise ratio of SSVEPs. The effects of sildenafil were dependent on the wavelength condition in both assays. Our results support the observation that while PDE6 is a key player in phototransduction, near full inhibition of PDE6 is not enough to abolish the complex process of visual processing. Taken together, VEPs and SSVEPs are effective in demonstrating progressive effects of drug-induced changes in visual processing in rats and as the same paradigms may be applied in humans, representing a promising tool for translational research.

AB - Photoreceptors are light-sensitive cells in the retina converting visual stimuli into electrochemical signals. These signals are evaluated and interpreted in the visual pathway, a process referred to as visual processing. Phosphodiesterase type 5 and 6 (PDE5 and 6) are abundant enzymes in retinal vessels and notably photoreceptors where PDE6 is exclusively present. The effects of the PDE inhibitor sildenafil on the visual system, have been studied using electroretinography and a variety of clinical visual tasks. Here we evaluate effects of sildenafil administration by electrophysiological recordings of flash visual evoked potentials (VEPs) and steady-state visual evoked potentials (SSVEPs) from key regions in the rodent visual pathway. Progressive changes were investigated in female Sprague-Dawley rats at 10 timepoints from 30 min to 28 h after peroral administration of sildenafil (50 mg/kg). Sildenafil caused a significant reduction in the amplitude of VEPs in both visual cortex and superior colliculus, and a significant delay of the VEPs as demonstrated by increased latency of several VEP peaks. Also, sildenafil-treatment significantly reduced the signal-to-noise ratio of SSVEPs. The effects of sildenafil were dependent on the wavelength condition in both assays. Our results support the observation that while PDE6 is a key player in phototransduction, near full inhibition of PDE6 is not enough to abolish the complex process of visual processing. Taken together, VEPs and SSVEPs are effective in demonstrating progressive effects of drug-induced changes in visual processing in rats and as the same paradigms may be applied in humans, representing a promising tool for translational research.

U2 - 10.1016/j.neuroscience.2020.06.033

DO - 10.1016/j.neuroscience.2020.06.033

M3 - Journal article

C2 - 32615234

VL - 441

SP - 131

EP - 141

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

ER -