Wakayama Symposium: Dependence of Corneal Epithelial Homeostasis on Transient Receptor Potential Function

Transient receptor potential (TRP) protein expression in the corneal epithelial layer contributes to the maintenance of tissue transparency. These proteins are members of a superfamily that form nonselective cation channels. This superfamily is a product of 28 different genes that are subdivided into six different subfamilies according to differences in amino acid sequence homology. The six subfamilies have very diverse functions. They are: 1) canonical (C); 2) vanilloid (V); 3) melastatin (M); 4) ankyrin (A); 5) polycystin (PP); 6) mucolipin (ML). TRP channels are composed of four monomeric subunits that are either members of the same or different subfamilies. In the corneal epithelium, C, V, and A subfamily subtype expression was identified. These include TRPV1-4, TRPC4, and TRPA1, which upon activation by either environmental stresses or selective ligands induce adaptive responses to stresses through transient increases in Ca2+ influx. Even though TRPs' Ca2+ permeability is variable relative to other cations, TRP activation is sufficient to stimulate mitogen-activated protein kinase cascade signaling through epidermal growth factor receptor transactivation. The host of TRP-mediated responses includes stimulation of cell proliferation, migration, regulatory volume behavior, and the release of a host of proinflammatory cytokines and chemoattractants. This review describes the multiple roles of these different channel subtypes in eliciting responses underlying maintenance of corneal epithelial function in health and disease.