Abstract
Purpose :
Elevated intraocular pressure (IOP) is an established risk factor for glaucoma. Steady-state IOP stems from a balance between aqueous humor (AH) production (AHp) and drainage. AHp results from the interaction among hydrostatic, osmotic and oncotic pressure differences determining a net fluid motion across ciliary epithelium (CE) bilayer from the stroma (S) to the aqueous side (AQ). The role of transcellular and paracellular (P) transport in AHp is difficult to disentangle experimentally, thus, we propose a mathematical model to investigate the contribution of each mechanism to AHp
Methods :
AHp is described by a compartment model solving iteratively the coupled interaction between ion electrodiffusion and AH fluid motion until convergence. The model includes S, a cell cytoplasm (C) representing the CE bilayer, P and AQ sides. A tight junction separates S from P to prevent large size proteins from flowing into the AQ. Ion transport is modeled through active and passive membrane transporters and carbonic anhydrase (CA)-mediated intracellular CO2 hydrolysis. Cell electroneutrality is ensured by a fixed intracellular negative charge. Simulations are performed under a transepithelial potential difference of 1mV (AQ negative) and hydrostatic pressures of 20 and 15 mmHg in S and AQ
Results :
Fig. 1 shows a scheme of AHp including membrane protein transporters driving primary active, secondary and passive ion transport. Transporters are not evenly distributed according to membrane diverse functional roles. Fig. 2 shows the scheme on which arrows represent the AH velocity vector across membranes. Model seems to indicate a much higher P velocity than C velocity. Results also indicate a flow of water from C into P and water recirculation from AQ into C. Model predicts a total AH volumetric flow rate (VFR) of 2.74 μL/min, in accordance with physiological data
Conclusions :
Simulations suggest that P transport significantly contributes to total AH VFR. They also indicate that osmotic pressure gradients determine a passive water flow from C into P and a water back flow from AQ into the cell. Results support the use of the proposed model as a mathematical virtual laboratory, noninvasively complementing the animal model, to test the efficacy of IOP lowering medications to decrease AHp
This is a 2021 ARVO Annual Meeting abstract.