title: Sildenafil Acutely Decreases Visual Responses in ON and OFF Retinal Ganglion Cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Sorbonne Universités, UPMC Univ Paris 06, Institut de la Vision, UMR_S968, Paris, France 2INSERM, U968, Paris, France 3CNRS, UMR_7210, Paris, France 4Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, C.
authors: João
authors: J
authors: Martins
authors: Sorbonne Universités, UPMC Univ Paris 06, Institut de la Vision, UMR_S968, Paris, France 2INSERM, U968, Paris, France 3CNRS, UMR_7210, Paris, France.
authors: Bogdan
authors: B
authors: Kolomiets
authors: Sorbonne Universités, UPMC Univ Paris 06, Institut de la Vision, UMR_S968, Paris, France 2INSERM, U968, Paris, France 3CNRS, UMR_7210, Paris, France.
authors: Romain
authors: R
authors: Caplette
authors: Sorbonne Universités, UPMC Univ Paris 06, Institut de la Vision, UMR_S968, Paris, France 2INSERM, U968, Paris, France 3CNRS, UMR_7210, Paris, France.
authors: José-Alain
authors: JA
authors: Sahel
authors: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal 5CNC.IBILI, University of Coimbra, Coimbra, Portugal.
authors: Miguel
authors: M
authors: Castelo-Branco
authors: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal 5CNC.IBILI, University of Coimbra, Coimbra, Portugal 6AIBILI, Coimbra, Portugal.
authors: António F
authors: AF
authors: Ambrósio
authors: Sorbonne Universités, UPMC Univ Paris 06, Institut de la Vision, UMR_S968, Paris, France 2INSERM, U968, Paris, France 3CNRS, UMR_7210, Paris, France 7Fondation Ophtalmologique Adolphe de Rothschild, Paris, France.
authors: Serge
authors: S
authors: Picaud
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000494:pharmacology*; D014786:Vision Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D000068677:Sildenafil Citrate