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一种用于睫状体上皮细胞电化学特性表征的理论方法。

A Theoretical Approach for the Electrochemical Characterization of Ciliary Epithelium.

作者信息

Sacco Riccardo, Guidoboni Giovanna, Jerome Joseph W, Bonifazi Giulio, Marazzi Nicholas M, Verticchio Vercellin Alice C, Lang Matthew S, Harris Alon

机构信息

Dipartimento di Matematica, Politecnico di Milano, 20133 Milano MI, Italy.

Department of Electrical Engineering and Computer Science, University of Missouri, Columbia , MO 65211, USA.

出版信息

Life (Basel). 2020 Jan 23;10(2):8. doi: 10.3390/life10020008.

Abstract

The ciliary epithelium (CE) is the primary site of aqueous humor (AH) production, which results from the combined action of ultrafiltration and ionic secretion. Modulation of ionic secretion is a fundamental target for drug therapy in glaucoma, and therefore it is important to identify the main factors contributing to it. As several ion transporters have been hypothesized as relevant players in CE physiology, we propose a theoretical approach to complement experimental methods in characterizing their role in the electrochemical and fluid-dynamical conditions of CE. As a first step, we compare two model configurations that differ by types of transporters included for ion exchange across the epithelial membrane, and by presence or absence of the intracellular production of carbonic acid mediated by the carbonic anhydrase enzyme. The proposed model configurations do not include neurohumoral mechanisms such as P2Y receptor-dependent, cAMP, or calcium-dependent pathways, which occur in the ciliary epithelium bilayer and influence the activity of ion transporters, pumps, and channels present in the cell membrane. Results suggest that one of the two configurations predicts sodium and potassium intracellular concentrations and transmembrane potential much more accurately than the other. Because of its quantitative prediction power, the proposed theoretical approach may help relate phenomena at the cellular scale, that cannot be accessed clinically, with phenomena occurring at the scale of the whole eye, for which clinical assessment is feasible.

摘要

睫状体上皮(CE)是房水(AH)生成的主要部位,房水生成是超滤和离子分泌共同作用的结果。调节离子分泌是青光眼药物治疗的一个基本靶点,因此确定促成离子分泌的主要因素很重要。由于几种离子转运体被认为是CE生理学中的相关参与者,我们提出一种理论方法来补充实验方法,以表征它们在CE的电化学和流体动力学条件中的作用。作为第一步,我们比较了两种模型配置,这两种配置的不同之处在于跨上皮膜进行离子交换所包含的转运体类型,以及是否存在由碳酸酐酶介导的细胞内碳酸生成。所提出的模型配置不包括神经体液机制,如睫状体上皮双层中发生的P2Y受体依赖性、cAMP或钙依赖性途径,这些途径会影响细胞膜中存在的离子转运体、泵和通道的活性。结果表明,两种配置中的一种比另一种更准确地预测钠和钾的细胞内浓度以及跨膜电位。由于其定量预测能力,所提出的理论方法可能有助于将临床上无法获取的细胞尺度现象与全眼尺度上发生的现象联系起来,而全眼尺度现象的临床评估是可行的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ecf/7175328/26ea47e8b9d6/life-10-00008-g001.jpg

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