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Giovanna Guidoboni, Giulio Bonifazi, Riccardo Sacco, Anita Layton, Sarah D Olson, Maila C Brucal Hallare, Brent A Siesky, Carlo Bruttini, Alice Chandra Verticchio Vercellin, Alon Harris; Electrochemical characterization of ciliary epithelium physiology: a theoretical approach. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3202. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The ciliary epithelium (CE) is the primary site of aqueous humor (AH) production, which results from the combined action of ultrafiltration and active ionic secretion. The modulation of ionic secretion is an important target for drug therapy in glaucoma, and therefore it is important to identify the main factors contributing to it. Since several ion transporters have been hypothesized as important players in CE physiology, we propose a theoretical approach to characterize their role in determining the electro-chemical and fluid-dynamical CE conditions.
We consider two different models (M0 and M1) for the same fundamental CE unit composed of one pigmented epithelial cell and one non-pigmented epithelial cell (Fig. 1). The CE unit (I) is located between the stroma (S) and the posterior chamber (P). In M0, we include: (i) the Na+-Cl--K+ symporter and the K+ uniporter on the S-CE membrane; and (ii) the Na+-K+ pump and the K+ and Cl- uniporters on the CE-P membrane (Fig.1a). M1 is an enrichment of M0 to include also: (i) the Cl--HCO3- and Na+-H+ antiporters on the S-CE membrane; (ii) the Cl--HCO3- antiporter on the CE-P membrane; and (iii) carbonic anhydrase reaction inside CE (Fig.1b).
Starting from available data on ion concentrations on the S and P sides, balance equations for mass and electric charge are utilized to calculate the electro-chemical variables characterizing CE in the assumptions of M0 and M1. Fig. 2 shows a comparison between experimental data and model predictions for (i) intracellular concentrations of Na+ and K+, and (ii) magnitudes of the transmembrane electric potential. M1 results are of the same order of magnitude as experimental data, thereby providing evidence that the Cl--HCO3- and Na+-H+ antiporters on the S-CE membrane, the Cl--HCO3- antiporter on the CE-P membrane, and the carbonic anhydrase reaction play a crucial role in determining the CE electro-chemical conditions.
This innovative mathematical modeling may enhance our understanding of aqueous humor dynamics and pathophysiology. Our model holds promise for assisting in diagnosing diseases of the eye and for testing new ophthalmic medications.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Fig. 1: Schematic representation of model M0 (a) and model M1 (b).
Fig. 2: Comparison between experimental data and model predictions.  Bowler et al (1996);  Wiederholt et al (1986);  Wu et al 2003
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