Transient receptor potential (TRP) ion channels mediate a variety of sensations including thermal stimuli. The channels also react to multiple ligands: for example, TRPV1 channels respond to heat as well as to ligands which elicit a hot sensation such as capsaicin, whereas TRPM8 channels respond to cold and also to ligands which elicit a cool sensation such as menthol. Since TRP channels are expressed on sensory neurons, a number of groups are developing selective channel modulators for the treatment of pain.
Researchers led by a team at the Instituto de Neurociencias de Alicante have now shown that TRPM8 channels in the eye also regulate basal tear secretion. In studies in mice, the researchers found that cooling of the eye surface by 1-2°C by evaporation of the tear film can induce production of more tears by stimulation of TRPM8 in nerve endings in the cornea. In mice lacking TRPM8, the cornea was insensitive to cooling and the basal rate of tear production was greatly reduced. Tear production caused by exposure to irritants which is mediated by other channels such as TRPV1 was, however, unaffected in the TRPM8 deficient mice. In normal mice, tear secretion could also be decreased by raising the temperature of the cornea to 33-36°C. Tear production in humans is also regulated by cold – the basal rate of tear production is significantly lower at 43°C than at 18-20°C.
The study, which is published in the journal Nature Medicine, indicates that TRPM8 contributes to the regulation of basal tear flow and opens new possibilities for the treatment of dry eye syndrome by increasing tear secretion. Dry mucosal surfaces, including dry eye syndrome, are a common problem, particularly for the elderly with up to one third of people over the age of sixty five estimated to have dry eyes.