Blood flow mechanics and oxygen transport and delivery in the retinal microcirculation: multiscale mathematical modeling and numerical simulation

The scientific community continues to accrue evidence that blood flow alterations and ischemic conditions in the retina play an important role in the pathogenesis of ocular diseases. Many factors influence retinal hemodynamics and tissue oxygenation, including blood pressure, blood rheology, oxygen arterial permeability and tissue metabolic demand. Since the influence of these factors on the retinal circulation is difficult to isolate in vivo, we propose here a novel mathematical and computational model describing the coupling between blood flow mechanics and oxygen (O2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\hbox {O}_2$$\end{document}) transport in the retina. Albeit in a simplified manner, the model accounts for the three-dimensional anatomical structure of the retina, consisting in a layered tissue nourished by an arteriolar/venular network laying on the surface proximal to the vitreous. Capillary plexi, originating from terminal arterioles and converging into smaller venules, are embedded in two distinct tissue layers. Arteriolar and venular networks are represented by fractal trees, whereas capillary plexi are represented using a simplified lumped description. In the model, O2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\hbox {O}_2$$\end{document} is transported along the vasculature and delivered to the tissue at a rate that depends on the metabolic demand of the various tissue layers. First, the model is validated against available experimental results to identify baseline conditions. Then, a sensitivity analysis is performed to quantify the influence of blood pressure, blood rheology, oxygen arterial permeability and tissue oxygen demand on the O2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\hbox {O}_2$$\end{document} distribution within the blood vessels and in the tissue. This analysis shows that: (1) systemic arterial blood pressure has a strong influence on the O2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\hbox {O}_2$$\end{document} profiles in both blood and tissue; (2) plasma viscosity and metabolic consumption rates have a strong influence on the O2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\hbox {O}_2$$\end{document} tension at the level of the retinal ganglion cells; and (3) arterial O2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\hbox {O}_2$$\end{document} permeability has a strong influence on the O2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\hbox {O}_2$$\end{document} saturation in the retinal arterioles.