A Theoretical Study of Aqueous Humor Secretion Based on a Continuum Model Coupling Electrochemical and Fluid-Dynamical Transmembrane Mechanisms

TL;DR

This paper introduces a comprehensive theoretical model coupling electrochemical and fluid dynamics to simulate aqueous humor secretion, providing insights into ionic pump functions relevant for glaucoma treatment.

Contribution

It presents a novel finite element model at the cellular level that accurately predicts ionic pump behavior and membrane potentials, validated against experimental data.

Findings

Model accurately predicts ionic pump functionality.

Theoretical membrane potentials match experimental data.

Provides a foundation for future molecular studies on AH production.

Abstract

Intraocular pressure, resulting from the balance of aqueous humor (AH) production and drainage, is the only approved treatable risk factor in glaucoma. AH production is determined by the concurrent function of ionic pumps and aquaporins in the ciliary processes but their individual contribution is difficult to characterize experimentally. In this work, we propose a novel unified modeling and computational framework for the finite element simulation of the role of the main ionic pumps involved in AH secretion, namely, the sodium potassium pump, the calcium-sodium pump, the anion channel and the hydrogenate-sodium pump. The theoretical model is developed at the cellular scale and is based on the coupling between electrochemical and fluid-dynamical transmembrane mechanisms characterized by a novel description of the electric pressure exerted by the ions on the intrachannel fluid that includes electrochemical and osmotic corrections. Considering a realistic geometry of the ionic pumps, the proposed model is demonstrated to correctly predict their functionality as a function of (1) the permanent electric charge density over the channel pump surface; (2) the osmotic gradient coefficient; (3) the stoichiometric ratio between the ionic pump currents enforced at the inlet and outlet sections of the channel. In particular, theoretical predictions of the transepithelial membrane potential for each simulated pump/channel allow us to perform a first significant model comparison with experimental data for monkeys. This is a significant step for future multidisciplinary studies on the action of molecules on AH production.