Detection of retinal dysfunction induced by HCN channel inhibitors using multistep light stimulus and long-duration light stimulus ERG in rats.

Ivabradine, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel inhibitor, has been reported to induce photosensitivity-related visual disturbances such as phosphene in humans. Ivabradine-induced visual disturbances are caused by inhibition of HCN channels in the retina, and the mechanisms have been verified using HCN channel knockout mice and electroretinography (ERG). However, in rats, classical ERG using single flash light stimulus with standard analyses of waveform amplitude and latency has not revealed abnormal retinal function after administration of ivabradine.

Use of an alternating current amplifier when recording the ERG c-wave to evaluate the function of retinal pigment epithelial cells in rats.

Purpose: We studied the conditions under which c-waves of the electroretinogram (ERG), that represent retinal pigment epithelium (RPE) function, were detectable using an alternating current (AC) amplifier and whether the c-wave recorded using an AC amplifier was useful for evaluating RPE function.

Methods: We recorded ERG responses in rats to 5 s stimuli under the conditions in which the low-cut frequency and the stimulus luminance were varied. In addition, changes in ERGs were studied after intravenous injection of sodium iodate (SI) to induce RPE degeneration.

Effects of microsampling on toxicity assessment of hematotoxic compounds in a general toxicity study in rats.

Microsampling (MS) has been increasingly used in toxicity studies reducing animal use for toxicokinetic analysis. However, especially for drugs with hematotoxic properties, the potential effects of MS on hematological parameters and subsequent toxicity assessment should be considered, while such properties are frequently unknown at the discovery stage. Here, we conducted a rat 2-week study of hematotoxic compounds and evaluated the effects of MS on toxicity assessment.

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.