April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Effects of sildenafil on primate retinas
Author Affiliations & Notes
  • Thuy Doan
    Department of Ophthalmology, University of Washington, Seattle, WA
  • Felice Dunn
    Department of Biological Structure, University of Washington, Seattle, WA
  • Fred Rieke
    Department of Physiology and Biophysics, University of Washington, Seattle, WA
    Howard Hughes Medical Institute, Seattle, WA
  • Footnotes
    Commercial Relationships Thuy Doan, None; Felice Dunn, None; Fred Rieke, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1887. doi:
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      Thuy Doan, Felice Dunn, Fred Rieke; Effects of sildenafil on primate retinas. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1887.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Phosphodiesterase type-5 inhibitors (PDE5), such as sildenafil, are widely used for the treatments of erectile dysfunction and arterial pulmonary hypertension. It has been documented that ingestion of PDE5 inhibitors can lead to visual disturbances, attributed to the nonspecific inhibition of PDE6 in rod and cone photoreceptors. However, human retinas have been shown to express PDE5 in the bipolar cell layer and inhibition at this site may contribute to the visual disturbances with sildenafil intake. In this study, we sought to quantify the direct effects of sildenafil on the electroretinogram (ERG) responses in primate retinas.

Methods: Primate retinas (Macaca fascilaris, Macaca nemestrina, and Macaca mulatta) were obtained through the Tissue Distribution Program of the Regional Primate Research Center and in accordance with the Institutional Animal Care and Use Committee at the University of Washington. In-vitro ERGs (Azevedo and Rieke, 2011) were used to determine the changes in the transretinal potential in response to light stimulation under application of various concentrations of sildenafil and drug washout conditions.

Results: Application of sildenafil reduced the amplitudes of the ERG a- and b-waves. The a- and b-wave implicit times also were prolonged in the presence of sildenafil. Sildenafil washout led to the partial recovery of both the a- and b-wave amplitudes and implicit times.

Conclusions: We found that sildenafil reduced the amplitudes and prolonged the kinetics of the a- and b-wave ERG responses. Responses were partially reversible for the duration of our recordings. Our experiments also demonstrate that in vitro ERG recordings in primate retinas may be an effective and useful technique for characterizing the effects of retinal drug toxicity in humans. The first two authors contributed equally.

Keywords: 688 retina • 503 drug toxicity/drug effects  

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