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Friday 01 April 2005

CFTR-regulated chloride transport at the ocular surface in living mice measured by potential differences.

By: Levin MH, Verkman AS.

Invest Ophthalmol Vis Sci 2005 Apr;46(4):1428-34

PURPOSE: To define the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in Cl(-) secretion at the mouse ocular surface in vivo. METHODS: Open-circuit potential differences (PDs) across the fluid-bathed ocular surface were measured in anesthetized wild-type and cystic fibrosis (CF) mice in response to Cl(-) ion substitution and transport agonists and inhibitors. RESULTS: Basal ocular surface PD was -23 +/- 1 mV (SE; 20 wild-type mice), depolarizing to -16 +/- 2 mV after amiloride, then hyperpolarizing to -34 +/- 3 mV after low Cl(-). CFTR activation by forskolin or a selective activator caused further sustained hyperpolarization to -50 to -60 mV. UTP produced a comparable but transient hyperpolarization. The CFTR inhibitors CFTR(inh)-172 and GlyH-101 largely reversed agonist- but not low Cl(-)-induced hyperpolarizations. PD in CF mice hyperpolarized by 2.1 mV after low Cl(-) and was insensitive to CFTR activators or inhibitors. CONCLUSIONS: CFTR provides a major pathway for mouse ocular surface Cl(-) secretion, suggesting the application of CFTR activators as therapy for dry eye. Amiloride-sensitive Na(+) transporters facilitate Na(+) absorption. PD measurements provide a robust and reproducible means of assessing ocular surface ion transporting mechanisms.

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