Abstract
Maintenance of intracellular Ca2+ levels at orders of magnitude below those in the extracellular environment is a requisite for preserving cell viability. Membrane channels contribute to such control through modulating their time-dependent opening and closing behaviour. Such regulation requires Ca2+ to serve as a second messenger mediating receptor control of numerous life-sustaining responses. Transient receptor potential (TRP) channels signal transduce a wide variety of different sensory stimuli to induce responses modulating cellular function. These channels are non-selective cation channels with variable Ca2+ selectivity having extensive sequence homology. They constitute a superfamily made up of 28 different members that are subdivided into 7 different subfamilies based on differences in sequence homology. Some of these TRP channel isotypes are expressed in the eye and localized to both neuronal and non-neuronal cell membranes. Their activation generates intracellular Ca2+ transients and other downstream-linked signalling events that affect numerous responses required for visual function. As there is an association between changes in functional TRP expression in various ocular diseases, there are efforts underway to determine if these channels can be used as drug targets to reverse declines in ocular function. We review here our current knowledge about the expression, function and regulation of TRPs in different eye tissues in health and disease. Furthermore, some of the remaining hurdles are described to developing safe and efficacious TRP channel modulators for use in a clinical setting.
Highlights
TRP channel relevance to ocular function One of the reasons why ocular transient receptor potential (TRP) channels are essential for maintaining normal vision is that some of their subtypes transduce environmental stresses into cell signalling events to control different physiological responses that alter cellular function
To shed some light on this complex question, we review literature describing ocular TRP channel functional expression in the cornea, conjunctival epithelium, uvea, lens and retina
As there is an association between aberrant TRP channel expression and human disease, these regulators of Ca2+ influx may be potential drug targets for usage in a clinical setting
Summary
TRP channel relevance to ocular function One of the reasons why ocular transient receptor potential (TRP) channels are essential for maintaining normal vision is that some of their subtypes transduce environmental stresses into cell signalling events to control different physiological responses that alter cellular function. Functional TRP expression has been identified in every ocular tissue eliciting responses to a host of sensory Changes in membrane stretch and exposure to an anisosmotic challenge (such as TRPV1 and TRPV4) as well as kinase-induced channel phosphorylation all lead to TRP activation whereas cooling directly can activate TRPM8 [16,17,18].
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