A THEORETICAL STUDY OF AQUEOUS HUMOR SECRETION BASED ON A CONTINUUM MODEL COUPLING ELECTROCHEMICAL AND FLUID-DYNAMICAL TRANSMEMBRANE MECHANISMS
A THEORETICAL STUDY OF AQUEOUS HUMOR SECRETION BASED ON A CONTINUUM MODEL COUPLING ELECTROCHEMICAL AND FLUID-DYNAMICAL TRANSMEMBRANE MECHANISMS
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DOI：
10.2140/camcos.2019.14.65
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发表时间：
2019-01-01
影响因子：
2.1
通讯作者：
Harris, Alon
中科院分区：
文献类型：
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作者：
Sala, Lorenzo;Mauri, Aurelio Giancarlo;Harris, Alon
眼内压是由房水（AH）的产生和排出平衡引起的，是青光眼中唯一被批准的可治疗的风险因素。AH的产生是由纤毛过程中的离子泵和水通道蛋白的共同作用决定的，但它们各自的贡献很难通过实验来表征。在这项工作中，我们提出了一种新的统一建模和计算框架的有限元模拟的作用，主要的离子泵和交换器参与AH分泌，即钠-钾泵，钙-钠交换器，氯-碳酸氢盐交换器，和钠-质子交换器。理论模型是在细胞尺度上开发的，并且是基于电化学和流体动力学跨膜机制之间的耦合，其特征在于由离子对孔内流体施加的包括电化学和渗透校正的电压的新颖描述。考虑到一个现实的几何形状的离子泵，所提出的模型被证明是正确的预测其功能的函数（1）的永久电荷密度在孔表面，（2）的渗透梯度系数，和（3）的化学计量比之间的离子泵电流在入口和出口部分的孔。特别是，每个模拟泵/交换器的跨上皮膜电位的理论预测，使我们能够执行第一个显着的模型与猴子的实验数据进行比较。这是一个重要的一步，为未来的多学科研究的行动分子AH生产。
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 ion 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 ion pumps and exchangers involved in AH secretion, namely, the sodium-potassium pump, the calcium-sodium exchanger, the chloride-bicarbonate exchanger, and the sodium-proton exchanger. 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 intrapore fluid that includes electrochemical and osmotic corrections. Considering a realistic geometry of the ion pumps, the proposed model is demonstrated to correctly predict their functionality as a function of (1) the permanent electric charge density over the pore surface, (2) the osmotic gradient coefficient, and (3) the stoichiometric ratio between the ion pump currents enforced at the inlet and outlet sections of the pore. In particular, theoretical predictions of the transepithelial membrane potential for each simulated pump/exchanger 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.