Availability of multistep light stimulus method for evaluation of visual dysfunctions.
In the field of drug safety research, electroretinography (ERG) is commonly conducted according to the international standard method propounded by the International Society for Clinical Electrophysiology of Vision (ISCEV) in recent years. However, various ERG methods other than the ISCEV standard method are also utilized depending on the intended purpose of the evaluation. In this study, we investigated the availability of a multistep light stimulus method for evaluation of rod function in Long-Evans rats using sildenafil, which is known to inhibit phosphodiesterase 6 (PDE6) in phototransduction and induce visual dysfunctions in humans. Sildenafil was orally administered to female Long-Evans rats at doses of 15, 50, and 150 mg/kg, and ERG was recorded at 1.5 h after treatment. In addition to a - 2.0 log cd·s/m2 stimulus corresponding to dark-adapted 0.01 ERG in the ISCEV standard method, light stimulus intensities of -4.5, -4.0, -3.0, -1.0, 0.0, and +1.0 log cd·s/m2 were applied for multistep ERG recording. The amplitude and implicit time of the a-wave were decreased and prolonged, respectively, at doses of ≥50 mg/kg. The amplitude and implicit time of the b-wave were decreased and prolonged, respectively, at all doses. However, the b-wave at 15 mg/kg was only diminished or attenuated at ≤ - 3.0 log cd·s/m2, as weaker stimuli than dark-adapted 0.01 ERG in the ISCEV standard protocol. These findings suggest that sildenafil triggers visual dysfunctions through PDE6 inhibition, and indicate that the multistep light stimulus method is highly sensitive for detection of phototransduction abnormalities in retinal rod cells.