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 (i) types of transporters included for ion exchange across the epithelial membrane, and by (i) 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.
Highlights
The last ten years have witnessed a continuous increase in the development and use of theoretical investigation tools based on mathematical models and numerical algorithms for computer simulation in Ophthalmology
We have proposed a theoretical approach to link biophysical phenomena occurring at different length scales in the ciliary epithelium, which contributes to the production of aqueous humor
The reason at the basis of this contribution, which to the best of our knowledge is unique in the literature, is that the ciliary epithelium (CE) is the primary site of aqueous humor (AH) production, which results from the combined action of ultrafiltration and ionic secretion
Summary
The last ten years have witnessed a continuous increase in the development and use of theoretical investigation tools based on mathematical models and numerical algorithms for computer simulation in Ophthalmology (see [1] and references cited therein). In this paper we focus our attention on a specific region of the eye, the ciliary body, and, in particular, we investigate the physiology of ciliary epithelium (CE) and the mechanisms underlying the production of aqueous humor (AH). This choice is motivated by the fact that AH flow and its regulation significantly contribute to determining the level of intraocular pressure (IOP) [5,6]. AH production strongly relies on osmotic pressure gradients that are generated across the CE by active ionic secretion, which represents a fundamental target for drug therapy in glaucoma. Since several ion transporters have been hypothesized as important players in the ionic secretion across the CE, we propose a theoretical approach to help characterize their role
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