Role of ion channels in the functional response of conjunctival goblet cells to dry eye

Optimal vision requires an ocular surface with a stable tear film whose many critical tasks include providing >70% of the eye's refractive power. However for millions, tear film instability produces uncomfortable sight-impairing dry eye. Despite the multitude of etiologies for dry eye, a universal hallmark is hyperosmolarity of the tear film. Presently, knowledge of how the ocular surface responds to hyperosmolarity remains incomplete with little understood about the role of ion channels. This bioelectric analysis focused on conjunctival goblet cells whose release of tear-stabilizing mucin is a key adaptive response to dry eye. In freshly excised rat conjunctiva, perforated-patch recordings demonstrated that a {greater than or equal to}10% rise in osmolarity triggers goblet cells to rapidly generate a ~15-mV hyperpolarization due to the oxidant-dependent activation of KATP channels. High-resolution membrane capacitance measurements used to monitor exocytosis revealed that this hyperpolarization results in...