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Mariia Dvoriashyna, Alexander J.E. Foss, Eamonn A. Gaffney, Oliver E. Jensen, Rodolfo Repetto; Mathematical Model of Fluid and Ion Transport across the Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3263.
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Reasons of failure of retinal pigment epithelium (RPE) pumping are poorly understood. Such failure leads to fluid accumulation in the sub-retinal space, which is associated with formation and development of age related macular degeneration and diabetic macular edema. Understanding the mechanisms that are responsible for fluid transport across the RPE is important for manipulation of the flow and prevention of fluid accumulation. Quantifying and determining the relative significance of such mechanisms is the purpose of the present work.
The proposed mathematical model contemplates osmosis and electroosmosis as possible mechanisms of water transport. Osmosis is governed by spatial variations in ion concentrations, which we obtain by solving the electrodiffusive ion transport problem in the tissue. Electroosmosis can occur in the gap between adjacent cells as a result of interaction between the electric field and the charges located in the electrical double layer (EDL). To model such flow we resolve the EDL to find spatial charge density and the electric field is obtained from the solution of the electrodiffusive ion transport problem. We also account for the conservation of the cell volume, which governs the concentration of negative charges in the cell and thus fully couples ion and fluid transport.
The model predicts ion concentrations in the cell and apical and basolateral membrane potentials, the values of which are close to those observed in experimental practice. We also find the distribution of ion concentrations in the gap between two adjacent cells, that drives a local osmotic flow, and predict that such flow largely dominates electroosmosis. Total transepithelial flux per unit surface is directed from the sub-retinal space to the choroid and is estimated to be ≈1.5×10-8 m/s, which is comparable with the measured values.
The proposed mathematical model couples cellular ion and fluid transport and applies it to determine the mechanisms that drive fluid across the RPE. Ion concentration gradient in the gap between two adjacent cells generates osmotic flow, which is two orders of magnitude larger than the electoosmotic one and comparable to the flow measured across the RPE. Osmosis is thus predicted to be the main driver of transepithelial fluid flow in the RPE, within a framework that also demonstrates the importance of spatial variation within the cleft gap.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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