July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018

A theoretical study of the role of conformational properties of transepithelial ion pumps on aqueous humor production
Author Affiliations & Notes
  • Riccardo Sacco
    Mathematics, Politecnico di Milano, Italy, Milan, Italy
  • Lorenzo Sala
    Université de Strasbourg, CNRS, IRMA, Strasbourg, France
  • Aurelio Giancarlo Mauri
    Mathematics, Politecnico di Milano, Italy, Milan, Italy
  • Dario Messenio
    Eye Clinic, Department of Clinical Science, Luigi Sacco Hospital, University of Milan, Milan, Italy
  • Giovanna Guidoboni
    Department of Electrical Engineering and Computer Science, College of Engineering, University of Missouri, Columbia, Missouri, United States
  • Brent Siesky
    Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Alon Harris
    Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Footnotes
    Commercial Relationships   Riccardo Sacco, None; Lorenzo Sala, None; Aurelio Mauri, None; Dario Messenio, None; Giovanna Guidoboni, None; Brent Siesky, None; Alon Harris, AdOM (C), AdOM (I), CIPLA (C), Nano Retina (I), Oxymap (I)
  • Footnotes
    Support  This work has been partially supported by Micron Semiconductor Italia S.r.l., statement of work #4505462139: ”Modeling of tunneling and charging dynamics”, by Ministère de l’Enseignement supérieur et de la Recherche (France), by NSF DMS-1224195, LabEx IRMIA (France), a grant from Research to Prevent Blindness (RPB, NY, USA) and by Research to Prevent Blindness (RPB, NY, USA).
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1656. doi:
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      Riccardo Sacco, Lorenzo Sala, Aurelio Giancarlo Mauri, Dario Messenio, Giovanna Guidoboni, Brent Siesky, Alon Harris;
      A theoretical study of the role of conformational properties of transepithelial ion pumps on aqueous humor production. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1656.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose :
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 mathematical model to investigate the role of conformational properties of Na+-K+, Ca2+-Na+, Cl--HCO3- and Na+-H+ ion pumps on AH production.

Methods :
Ion pump function is modeled by coupling a velocity-extended electrochemical module for ion motion and an electrochemically driven fluid module for AH flow. Time-dependent simulations are conducted to study ion pump features as a function of (1) permanent electric charge density over the channel pump surface; (2) osmotic gradient coefficient; (3) stoichiometric ratio between ion pump currents at channel inlet and outlet.

Results :
Fig. 1 shows the steady-state electric potential V along the channel axis Z. Potential drop is due only to the electric field generated by permanent surface charge density. Despite remarkably different profiles of V inside the channel, the predicted transmembrane potential Vm=V(Z=10nm)-V(Z=0nm) is for all pumps in good agreement with the range [-2.7, -2.3] mV experimentally measured on monkeys. Fig. 2 shows the steady-state AH velocity along Z. Fluid motion is due only to electric pressure exerted by the ions. Model predicts a positive AH flow in all channel length for Na+-K+ and Ca2+-Na+ pumps, a positive AH flow in the central region for Cl--HCO3- pump and AH flow inversion at Z=6.5nm for Na+-H+ pump.

Conclusions :
The proposed mathematical model allowed us to simulate the four main ion pumps involved in AH production. Predicted transepithelial potential and AH flow are in good agreement with measured data and biophysical intuition. Results support adopting the theoretical tool as a virtual laboratory to verify conjectures, compare different scenarios and complement the indispensable animal model in patient-specific therapy design.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 


Fig. 1. Spatial distribution of electric potential along channel axis. Blue: K+-Na+ pump. Black: Ca2+-Na+ pump. Green: Cl--HCO3- pump. Red: H+-Na+ pump.


Fig. 1. Spatial distribution of electric potential along channel axis. Blue: K+-Na+ pump. Black: Ca2+-Na+ pump. Green: Cl--HCO3- pump. Red: H+-Na+ pump.

 


Fig. 2. Spatial distribution of AH velocity along channel axis. Blue: K+-Na+ pump. Black: Ca2+-Na+ pump. Green: Cl--HCO3- pump. Red: H+-Na+ pump.


Fig. 2. Spatial distribution of AH velocity along channel axis. Blue: K+-Na+ pump. Black: Ca2+-Na+ pump. Green: Cl--HCO3- pump. Red: H+-Na+ pump.

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