Potential difference measurements of ocular surface Na+ absorption analyzed using an electrokinetic model

Area of Science:

• Ocular surface physiology
• Epithelial transport mechanisms
• Mathematical modeling of biological systems

Background:

• Corneal and conjunctival epithelia facilitate transcellular Na+ absorption and Cl- secretion, driving ocular surface fluid movement.
• Previous research identified Ca2+- and cAMP-sensitive Cl- channels, including the cystic fibrosis transmembrane conductance regulator (CFTR), in ocular surface Cl- transport.

Purpose of the Study:

• To identify the specific transporting mechanisms responsible for Na+ absorption across the ocular surface epithelium.
• To develop a mathematical model to quantify ocular surface ion transport and the electrochemical coupling between different transport processes.

Main Methods:

• Measured potential differences (PDs) across the ocular surface in wild-type and CF mice using ion substitution and transporter modulators.
• Developed an electrokinetic model of the ocular surface epithelium to simulate PD measurements and cell ion concentrations.

Main Results:

• Na+ replacement caused depolarization blocked by amiloride, with greater effect in CF mice, indicating amiloride-sensitive Na+ channels.
• D-glucose, glycine, and L-arginine induced Na+-dependent hyperpolarizations, suggesting coupled transport mechanisms.
• The developed epithelial transport model accurately reproduced experimental PD measurements.

Conclusions:

• Potential difference measurements and modeling quantitatively defined Na+ and Cl- transport roles in ocular surface ion and fluid movement.
• CFTR-dependent changes in apparent epithelial Na+ channel (ENaC) activity can be explained by electrochemical coupling.
• ENaC inhibitors and CFTR activators show potential as therapies for dry eye syndromes by enhancing ocular surface fluid secretion.