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The ocular surface is constantly covered with a layer of tears that play essential roles in maintain-ing the health and function of the eye by providing lubrication, nutrients, and protection to the eye.Changes in the volume and/or composition of tears may result in dry eye, which arises from diverse eti-ologies, e.g., deficiencies in fluid or lipid composition.Aqueous-deficient dry eye is caused by abnor-malities in the production of aqueous tears by the lacrimal gland (LG), including those associated withSj(o)grens syndrome.LG is the major source of tears, which function is mediated by an array of ion transporters, chan-nels, and aquaporins, such as cystic fibrosis transmembrane conductance regulator (CFTR), which generate the electrogenic gradient that causes an osmotic force that drives water into the lumen.Apical Cl-secretion across epithelia provides the primary driving force for LG fluid secretion, and activation of apical anion channels, especially Cl-channels, is the rate-limiting step for fluid secretion by most exo-crine glands, including LG.