Pathophysiological Role and Drug Modulation of Calcium Transport in Ocular Surface Cells

The ocular surface structure and extraocular accessory organs constitute the ocular surface system, which includes the cornea, conjunctiva, eyelids, lacrimal organs, and lacrimal passages. This system is composed of, and stabilized by, the corneal epithelium, conjunctival cells, conjunctival goblet cells, lacrimal acinar cells and Tenon's fibroblasts, all of which maintain the healthy eyeball surface system. Ocular surface diseases are commonly referred to corneal and conjunctival disease and external ocular disease, resulting from damage to the ocular surface structure. A growing body of evidence has indicated that abnormal activation of the KCa3.1 channel and Ca2+/ calmodulin-dependent kinase initiates ocular injury. Signaling pathways downstream of the irregular Ca2+ influx induce cell progression and migration, and impair tight junctions, epithelial transport and secretory function. In this overview, we summarize the current knowledge regarding ocular surface disease in terms of physical and pathological alteration of the ocular system. We dissect in-depth, the mechanisms underlying disease progression, and we describe the current calcium transport therapeutics and the obstacles that remain to be solved. Finally, we summarize how to integrate the research results into clinical practice in the future.