Hydrogen sulfide: role in ion channel and transporter modulation in the eye

Abstract

Hydrogen sulfide (H2S), a colorless gas with a characteristic smell of rotten eggs, has been portrayed for decades as a toxic environmental pollutant. Since evidence of its basal production in mammalian tissues a decade ago, H2S has attracted substantial interest as a potential inorganic gaseous mediator with biological importance in cellular functions. Current research suggests that, next to its counterparts nitric oxide and carbon monoxide, H2S is an important multifunctional signaling molecule with pivotal regulatory roles in various physiological and pathophysiological processes as diverse as learning and memory, modulation of synaptic activities, cell survival, inflammation, and maintenance of vascular tone in the central nervous and cardiovascular systems. In contrast, there are few reports of a regulatory role of H2S in the eye. Accumulating reports on the pharmacological role of H2S in ocular tissues indicate the existence of a functional trans-sulfuration pathway and a potential physiological role for H2S as a gaseous neuromodulator in the eye. Thus, understanding the role of H2S in vision-related processes is imperative to our expanding knowledge of this molecule as a gaseous mediator in ocular tissues. This review aims to provide a comprehensive and current understanding of the potential role of H2S as a signaling molecule in the eye. This objective is achieved by discussing the involvement of H2S in the regulation of (1) ion channels such as calcium (L-type, T-type, and intracellular stores), potassium (KATP and small conductance channels) and chloride channels, (2) glutamate transporters such as EAAT1/GLAST and the L-cystine/glutamate antiporter. The role of H2S as an important mediator in cellular functions and physiological processes that are triggered by its interaction with ion channels/transporters in the eye will also be discussed.

Increased intracellular Cl− concentration promotes ongoing inflammation in airway epithelium

“…Hydrogen sulfide (H 2 S), the sulfhydrylcontaining gasotransmitter, reportedly mediated Cl − transportation in various cells. [30][31][32] Therefore, we determined whether H 2 S could influence on [Cl − ] i , thereby verifying its anti-inflammatory effects in airway epithelial cells. Sodium hydrosulfide (NaHS), the H 2 S donor, elicited a sustained increase in short-circuit current (I sc ) response as a consequence of Cl − secretion by activating CFTR via adenylate cyclase (AC)-cAMP pathway.…”

Hydrogen Sulfide Contributes to Retinal Neovascularization in Ischemia-Induced Retinopathy

“…Hydrogen sulfide (H 2 S) is a crucial gaseous signaling molecule that is involved in many physiological and pathologic conditions. 5 – 21 Three H 2 S-generating enzymes, cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), are responsible for H 2 S production in various types of tissues. 22 , 23 The role of H 2 S in retinal pathophysiological changes has been appreciated in the past decade.…”

“… 22 , 23 The role of H 2 S in retinal pathophysiological changes has been appreciated in the past decade. Studies discovered several protective properties of H 2 S in a variety of conditions, including protecting retina from light-induced degeneration by suppression of Ca 2+ influx, 10 attenuating excitotoxic neurotransmission, 9 protecting retinal neuronal cell apoptosis against NMDA or retinal ischemia-reperfusion–induced injury via its antioxidative activity, 11 , 12 , 24 inducing retinal vascular relaxation, 25 , 26 and alleviating retinal oxidative stress and inflammation in a rat model of streptozotocin-induced diabetes. 27 In spite of this progress, the function of H 2 S in neovascular disease in the retina is unknown, although increased plasma and vitreous H 2 S has been found in patients with proliferative diabetic retinopathy, 28 and H 2 S exhibits proangiogenic property in organs where ischemic vessel growth is beneficial.…”

Gasotransmitters: novel regulators of ion channels and transporters

“…This research topic summarizes currently available data on the regulation of ion channels and transporters by NO, CO, and H 2 S. Excellent review and research articles highlight the importance of gasotransmitter/ion channel interactions for vegetative physiology (Althaus, 2012; Peers, 2012; Pouokam and Diener, 2012), neurophysiology (Njie-Mbye et al, 2012; Peers, 2012; Takahashi et al, 2012; Wang et al, 2012), and explain gasotransmitter-induced signaling mechanisms (Wall et al, 2012). Furthermore, opinion articles from pioneers in gasotransmitter research (Kimura, 2012; Peers, 2012; Olson, 2013) give perspectives on important routes which should be followed in this field.…”