Polymodal roles of transient receptor potential channels in the control of ocular function

Maintenance of intracellular Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.