Cellular mechanisms underlying the pharmacological induction of phosphenes

Abstract

Visual sensations evoked by stimuli other than luminance changes are called phosphenes. Phosphenes may be an early symptom in a variety of diseases of the retina or of the visual pathways, but healthy individuals may perceive them as well. Phosphene‐like phenomena are perhaps the most common side effect reported in clinical pharmacology. Ivabradine, a novel anti‐anginal drug that reduces heart‐rate by inhibiting the hyperpolarization activated current expressed in cardiac sinoatrial node cells (If) induces phosphenes in some patients. One hypothesis is that ivabradine interacts with the visual system by inhibiting hyperpolarization‐activated current in retinal cells (Ih). An Ih current with properties similar to cardiac If has been reported in retinal neurones. Under normal circumstances most of the random fluctuations generated within the retinal circuits do not reach the level of conscious perception because they are filtered out. Presumably, filtering occurs mostly within the retina and one serious candidate for this action is the ability of Ih to act as a negative‐feedback mechanism. Ih activation in the membrane of visual cells causes dampening of responses to slow noisy inputs thus tuning the visual system to perceptually more relevant signals of higher frequency. Ih inhibition, by altering at the retinal synapses the filtering of signals generated by thermal breakdown of rhodopsin or other fluctuations, is expected to increase the probability of phosphene occurrence. It is the purpose of the present paper to outline and discuss the features of the visual system and the pharmacological conditions relevant to phosphene perception. British Journal of Pharmacology (2007) 150, 383–390. doi:

Phosphene perception is due to the ultra-weak photon emission produced in various parts of the visual system: glutamate in the focus

“…Phosphene-like phenomena are the common side effects of fever (high temperature) (Cervetto et al, 2007). Considering the mentioned findings, it supports that fever induces an elevated glutamate production that activates NMDARs.…”

“…Another peak is at 703 nm (Khan and Kasha, 1970) and approximately 1270 nm (Baker and Kanofsky, 1991 In addition, as mentioned, glutamate has a significant function in thermoregulation by means of the NMDA ionotropic receptors (Yoshimatsu et al, 1993;Paro et al, 2003), and there is a significant association between temperature and glutamate excitotoxicity (Campos et al, 2012). Thus, glutamate-related phosphene induction through UPE may also be a possible mechanism relating fever (high body temperature) and phosphenes (Cervetto et al, 2007).…”

“…The occurrence of phosphenes is also related to intoxications (drugs, alcohol, etc. ) or psychological conditions (Cervetto et al, 2007). Phosphenes are only perceived by blind people who have prior visual experience, suggesting that early visual experience is necessary to maintain any level of residual visual function (Merabet et al, 2003).…”

Hyperpolarization-Activated Cation Channels: From Genes to Function

“…A major obstacle of most existing agents is that they are not specific enough for sinoatrial (mainly HCN4-mediated) I h , but also block neuronal I h in several regions of the nervous system. For example, visual disturbances that result from block of retinal I h have been reported for several of these drugs (78). Moreover, some of the blockers may also interact with other ion channels.…”

Ivabradine: a new rate-limiting therapy for coronary artery disease and heart failure

“…Cross-reactivity with I h channels Hyperpolarization voltage-gated channels are not exclusive to pacemaker cells in the sinoatrial node but are also found in neuronal I h channel retinal and CNS tissues [Cervetto et al 2007]. Because of the lipophobic nature of the structure of ivabradine it does not cross the bloodbrain barrier.…”