Bemme Sebastian, Weick Michael, Gollisch Tim
Department of Ophthalmology, University Medical Center Göttingen, Göttingen, Germany.
Bernstein Center for Computational Neuroscience Göttingen, Göttingen, Germany.
Invest Ophthalmol Vis Sci. 2017 Sep 1;58(11):4754-4767. doi: 10.1167/iovs.17-21572.
Phosphene perception is a characteristic side effect of heart rate-reducing medication that acts on hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels. It is hypothesized that these phosphenes are caused by blocking HCN channels in photoreceptors and neurons of the retina, yet the underlying changes in visual signal processing in the retina caused by the HCN channel block are still unknown.
We examined the effects of pharmacologic HCN channel block on the encoding of visual signals in retinal ganglion cells by recording ganglion cell spiking activity from isolated mouse retinas mounted on multielectrode arrays. Spontaneous activity and responses to various visual stimuli were measured before, during, and after administration of 3 μM ivabradine.
Retinal ganglion cells generally showed slower response kinetics and reduced sensitivity to high temporal frequencies under ivabradine. Moreover, ivabradine differentially affected the sensitivity of On and Off ganglion cells. On cells showed reduced response gain, whereas Off cells experienced an increase in response threshold. In line with these differential effects, Off cells, in contrast to On cells, also showed reduced baseline activity during visual stimulation and reduced spontaneous activity. Furthermore, Off cells, but not On cells, showed increased burst-like spiking activity in the presence of ivabradine.
Our data suggest that pharmacologic HCN channel block in the retina leads to a shift in the relative activity of the On and Off pathways of the retina. We hypothesize that this imbalance may underlie the medication-induced perception of phosphenes.
光幻视是作用于超极化激活环核苷酸门控（HCN）离子通道的降心率药物的一种特征性副作用。据推测，这些光幻视是由视网膜光感受器和神经元中的HCN通道被阻断所致，然而，HCN通道阻断引起的视网膜视觉信号处理的潜在变化仍不清楚。
我们通过记录安装在多电极阵列上的离体小鼠视网膜神经节细胞的放电活动，研究了药理学上HCN通道阻断对视网膜神经节细胞视觉信号编码的影响。在给予3 μM伊伐布雷定之前、期间和之后，测量自发活动和对各种视觉刺激的反应。
在伊伐布雷定作用下，视网膜神经节细胞通常表现出较慢的反应动力学，对高时间频率的敏感性降低。此外，伊伐布雷定对开型和关型神经节细胞的敏感性有不同影响。开型细胞的反应增益降低，而关型细胞的反应阈值升高。与这些不同影响一致，与开型细胞相比关型细胞在视觉刺激期间的基线活动也降低，自发活动减少。此外，关型细胞而非开型细胞在存在伊伐布雷定的情况下表现出爆发样放电活动增加。
我们的数据表明，视网膜中药理学上的HCN通道阻断导致视网膜开型和关型通路相对活动的改变。我们推测这种失衡可能是药物诱导光幻视感知的基础。
