Effect of ivabradine on the activity of retinal ganglion cells

Abstract

Event Abstract Back to Event Effect of ivabradine on the activity of retinal ganglion cells Sebastian Bemme1*, Michael Weick1 and Tim Gollisch1 1 University Medical Center Göttingen, Department of Ophthalmology, Germany Ivabradine is a new bradycardic agent which was approved for symptomatic management of stable angina pectoris and acts by blocking of HCN4-channels in the sinoatrial node (1). About 15 % of patients treated with ivabradine report slight and completely reversible luminous phenomena (phosphenes), which occured after 2 month of medication (2). Ivabradine is thought to induce phosphenes by blocking hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels in photoreceptors. These channels play an important role in shaping the membrane potential after activation and are therefore thought to be essential for efficient encoding of stimuli at high-frequency (3). Blocking HCN channels causes prolonged hyperpolarization of photoreceptor inner segments, and knock-out studies revealed the importance of retinal HCN-channels for mesopic cone vision (4). Yet, experiments investigating the pharmacological induction of phosphenes by ivabradine have so far focused on histology, photoreceptor electrophysiology (5) or electroretinograms (6). Complementary to these studies, we here focus on the effect of ivabradine on the encoding of visual signals at the output stage of the retina that is in the activity of retinal ganglion cells. In particular, we search for spike pattern in RGC activity after administration of ivabradine that could underlie the reported phosphenes. To do so, we mounted isolated mouse retina on a 252-channel multielectrode array to record spikes from individual ganglion cells. We measured spontaneous activity as well as response to a series of light stimuli (steps in light intensity, different types of temporal and spatio-temporal flicker) before, during and after administration of 3 µM ivabradine. Preliminary results show altered spontaneous activity in RGCs during ivabradine administration, with ON-type RGCs primarily showing increased and OFF-type RGCs rather decreased spontaneous activation. We hypothesize that this imbalanced spontaneous activity by ON-type and OFF-type RGCs may contribute to luminous phenomena reported by patients treated with ivabradine. This work was supported by the German Initiative of Excellence, the International Human Frontier Science Program Organization, and the Deutsche Forschungsgemeinschaft (DFG-SFB 889).