A Theoretical Approach for the Electrochemical Characterization of Ciliary Epithelium

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.

Lymphatics in Eye Fluid Homeostasis: Minor Contributors or Significant Actors?

“…In the eye of mammals (Figure 1), the spaces between the cornea and the lens in the eye anterior segment are filled by aqueous humor, a transparent biological fluid. Aqueous humor is produced and secreted by the ciliary processes into the posterior chamber from where it moves to the anterior chamber after flowing through the pupil [3,7,8]. Aqueous humor formation results from a complex process of passive and active mechanisms which combine diffusion, filtration and secretion.…”

“…Secretion of aqueous humor into the posterior chamber is further achieved by fluid transfer through the ciliary epithelial cell bilayer. The active ion transport by the outer non-pigmented ciliary epithelial cell layer sets the aqueous humor ionic composition and generates the osmotic pressure gradient which constitutes the driving force at the origin of the secretion process [7,8]. On the other hand, vitreous humor, which constitutes the largest part of the human eye, fills the space between the lens and the retina in the posterior eye segment [9,10].…”

Neurodegenerative Disorders of the Eye and of the Brain: A Perspective on Their Fluid-Dynamical Connections and the Potential of Mechanism-Driven Modeling

“…Most of these models have focused on macroscale phenomena, with only few models accounting for their counterparts at levels of single cells and ion exchangers on the cellular membrane (Mauri et al, 2016;Sala et al, 2019a;Sacco et al, 2020). As a further note, to date, only few mechanism-driven models have included the dynamics of Aβ (Craft et al, 2002;Puri and Li, 2010;Das et al, 2011;Kyrtsos and Baras, 2015;Lorenzani, 2016, 2017).…”

“…Examples include models coupling biomechanics and hemodynamics (Guidoboni et al, 2014a , b , c ; Arciero et al, 2019 ; Sala, 2019 ) and models coupling hemodynamics and oxygenation (Arciero et al, 2013 , 2019 ; Causin et al, 2016 ; Carichino et al, 2016 ; Fry et al, 2018 ). Most of these models have focused on macroscale phenomena, with only few models accounting for their counterparts at levels of single cells and ion exchangers on the cellular membrane (Mauri et al, 2016 ; Sala et al, 2019a ; Sacco et al, 2020 ). As a further note, to date, only few mechanism-driven models have included the dynamics of Aβ (Craft et al, 2002 ; Puri and Li, 2010 ; Das et al, 2011 ; Kyrtsos and Baras, 2015 ; Franchi and Lorenzani, 2016 , 2017 ).…”

A Mathematical Model of Aqueous Humor Production and Composition

“…In a recent work, Sacco et al 16 proposed a more detailed model that takes into account the distribution of ion channels on the cell membrane (with the exception of the - channel, which was omitted). The authors impose the concentration of all species both on the stromal and PC sides of the CE and use the model to compute the concentration of all species in the cell.…”