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The ability of a cell to keep its volume constant irrespective of intra- and extracellular conditions is essential for cellular homeostasis and survival. The purpose of this study is to elaborate a theoretical model of cell volume homeostasis and to apply it to a simulation of human aqueous humor (AH) production. The model assumes a cell with a spherical shape and only radial deformation satisfying the property that the cell volume in rest conditions equals that of the cell couplets constituting the ciliary epithelium of the human eye. The cytoplasm is described as a homogeneous mixture containing fluid, ions, and neutral solutes whose evolution is determined by net production mechanisms occurring in the intracellular volume and by water and solute exchange across the membrane. Averaging the balance equations over the cell volume leads to a coupled system of nonlinear ordinary differential equations (ODEs) which are solved using the θ-method and the Matlab function ode15s. Simulation tests are conducted to characterize the set of parameters corresponding to baseline conditions in AH production. The model is subsequently used to investigate the relative importance of (a) impermeant charged proteins; (b) sodium–potassium (Na+/K+) pumps; (c) carbonic anhydrase (CA) in the AH production process; and (d) intraocular pressure. Results suggest that (a) and (b) play a role; (c) lacks significant weight, at least for low carbon dioxide values; and (d) plays a role for the elevated values of intraocular pressure. Model results describe a higher impact from charged proteins and Na+/K+ ATPase than CA on AH production and cellular volume. The computational virtual laboratory provides a method to further test in vivo experiments and machine learning-based data analysis toward the prevention and cure of ocular diseases such as glaucoma. 

Précis:The relationship between structural and hemodynamic parameters in patients with primary open angle glaucoma is strongest in the temporal region of the optic nerve. Purpose:To investigate the relationship between radial peripapillary capillary (RPC) vessel density (VD) and retinal nerve fiber layer (RNFL) thickness in quadrants and sectors of the optic nerve head (ONH) in patients with and without primary open angle glaucoma (POAG). Methods:In a cross-sectional prospective analysis, 191 subjects (80 early-stage POAG; 111 non-glaucomatous controls) were assessed for RNFL thickness and RPC VD in each quadrant [superior (S), inferior (I), nasal (N) and temporal (T)] and sector [inferior-temporal (IT), temporo-inferior (TI), temporo-superior (TS), superior-temporal (ST), inferior-nasal (IN), naso-inferior (NI), naso-superior (NS), and superior-nasal (SN) sectors] of the ONH through optical coherence tomography angiography (OCTA). Pearson correlations were used to test for associations between measurements, withP<0.05 considered statistically significant. Results:Significantly stronger positive correlations were found between RPC VD and RNFL thickness in the S, I, and T quadrants in POAG patients compared with non-glaucomatous controls (allP<0.05). The temporal quadrant in POAG patients displayed the largest difference in correlation compared with controls. A stronger positive correlation was also found between RPC VD and RNFL thickness in the temporal sectors of the ONH in POAG patients compared with controls, with the largest difference in the TS sector (allP<0.05). Conclusion:Early-stage POAG patients have a stronger relationship between RPC VD and RNFL in the temporal regions of the ONH compared with non-glaucomatous controls, with the TS sector demonstrating the largest difference between groups. Temporal sector VD loss may represent an early-stage biomarker for vascular-linked POAG disease.