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Impact of Second-Generation PDE 5 Inhibitor, Avanafil, on Retinal Function : Studies From Ex Vivo ERG
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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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en
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10
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Investigative Ophthalmology and Visual Science, Volume 66, issue 6, pp. 1-10
Abstract
Purpose: This study investigates whether avanafil, a second-generation phosphodiesterase 5 (PDE5) inhibitor, exhibits reduced off-target effects on retinal function compared to first-generation inhibitors, by quantifying its impact on photoreceptor and bipolar cell signaling using transretinal electroretinography (tERG). Methods: We conducted ex vivo tERG using wild-type C57BL/6J and Gnat−/− mice. The dark-adapted isolated retinas were stimulated with 530-nm full-field flashes of light while perfused with controlled avanafil concentrations at 0.1, 0.3, 1, 3, and 10 µM. The inhibition constant of avanafil for light-activated phosphodiesterase 6 (PDE6) was determined from flash responses for rods and cones. The effects of avanafil on bipolar cell signaling were also assessed. Results: Avanafil exhibited dose-dependent inhibition of rod and cone phototransduction, characterized by slower response kinetics and reduced amplitude of dim flash responses. The inhibition constants for light-activated PDE6 were determined to be 1.74 µM for rods and 6.3 µM for cones. This study demonstrated that avanafil does not inhibit spontaneous PDE6 activity, and it has a lower inhibitory effect on light-activated PDE6 compared to other PDE5 inhibitors like sildenafil and zaprinast. Additionally, we conclude that avanafil primarily impacts photoreceptor cells, with no significant direct effect on rod bipolar cell signaling. Conclusions: This study provides quantitative insights into avanafil's impact on retinal function, supporting the hypothesis that it has reduced off-target effects on PDE6 and retinal signaling.
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Saeid, S, Vinberg, F & Koskelainen, A 2025, 'Impact of Second-Generation PDE 5 Inhibitor, Avanafil, on Retinal Function : Studies From Ex Vivo ERG', Investigative Ophthalmology and Visual Science, vol. 66, no. 6, 14, pp. 1-10. https://doi.org/10.1167/iovs.66.6.14