The effects of the phosphodiesterase type V inhibitor sildenafil on human and bovine retinal function in vitro.
BACKGROUND
After the ingestion of sildenafil (Viagra), visual adverse events have been reported, possibly caused by an inhibition of the phototransduction cascade by sildenafil via phosphodiesterase (PDE 6). Therefore, we investigated the effects of sildenafil on photoreceptors and postsynaptic neurons of human and bovine retinas using the isolated superfused vertebrate retina technique.


METHODS
Human and bovine retina preparations were perfused with an oxygen preequilibrated standard solution. The electroretinogram (ERG) was recorded using Ag/AgCl electrodes. After recording stable ERG amplitudes, sildenafil was added to the solution for 45 min. Thereupon, the preparations were reperfused with standard solution for 240 min.


RESULTS
Following the application of sildenafil (3 microMol/l), the b-wave amplitude of bovine and human preparations was reduced continuously and disappeared completely. After reperfusion with the standard solution for 4 h, the b-wave amplitude did not recover completely. Using the same sildenafil concentration (3 microMol/l), the a-wave amplitude of the human retina was not totally abolished, but reduced to 21% of the initial amplitude and remained reduced at washout. For all retinal preparations, the implicit time of the ERG amplitudes remained significantly extended at the end of the washout.


CONCLUSIONS
Strong similarities were detected in the drug-induced changes of the ERG when comparing human and bovine retinas. The results suggest that sildenafil impairs retinal function at not only the level of the photoreceptors, but it also affects the neuronal network of the inner retina at concentrations of approximately 30-fold higher than at therapeutic plasma concentrations.
Lüke
Matthias
M
Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, 50931 Köln, Germany. matthias.lueke@med.uni-tuebingen.de
Szurman
Peter
P
Schneider
Toni
T
Lüke
Christoph
C
D000368:Aged; D000818:Animals; D002417:Cattle; D004596:Electroretinography / Q000187:drug effects*; D006801:Humans; D008297:Male; D010477:Perfusion; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*
D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate