Abstract
Purpose: :
To investigate the effects of long-term, high dose sildenafil administration on ERG responses and vision in PDE6A+/- dogs.Materials &
Methods: :
Five female PDE6A+/- dogs were assigned to two groups. Three dogs were dosed with sildenafil at 14.3 mg/kg per os once daily for four months. Two dogs received placebo. Ophthalmic examinations, fundus photography, electroretinography, and vision testing were performed monthly on all dogs during the pretreatment, treatment, and washout phases. Dark-adapted ERG intensity:response series and rod-mediated flicker responses were recorded followed by light adaptation and a light-adapted intensity:response series and cone flicker responses. The vision-testing device consisted of a junction box with four exit tunnels. The first-choice tunnel and exit time were recorded during repeated box exit attempts.
Results: :
No ophthalmoscopic abnormalities were identified. ERGs responses recorded from dogs receiving sildenafil had raised dark-adapted b-wave thresholds with an "unmasking" of the scotopic threshold response. Significantly decreased dark-adapted a- and b-wave amplitudes (P<0.001 and P=0.002, respectively) and increased implicit times (P=0.016 and P<0.001, respectively) were also noted. Naka-Rushton fit Vmax was decreased and K was increased during the treatment phase (P=0.002, and P<0.001, respectively). Recovery of the waveforms was observed at washout. Incorrect initial tunnel choice was significantly different between the groups at the lowest light intensity (0.002 cd/m2) during the treatment phase (P=0.022).
Keywords: retina • electroretinography: non-clinical • drug toxicity/drug effects