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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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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.
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.
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.
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.
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