Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis, 402 N. Blackford St., LD 270 D Indianapolis, IN 46202-3267, USA
Dr. Julia Arciero
Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis, 402 N. Blackford St., LD 270 D Indianapolis, IN 46202-3267, USA
Purpose. To study whether impaired retinal autoregulation is a risk factor for glaucoma, the relationship between vascular regulatory mechanisms and glaucoma progression needs to be investigated. In this study, a vascular wall mechanics model is used to predict the relative importance of regulatory mechanisms in achieving retinal autoregulation. Methods. Resistance vessels are assumed to respond to changes in pressure, shear stress, carbon dioxide (CO2), and the downstream metabolic state communicated via conducted responses. Model parameters governing wall tension are fit to pressure and diameter data from porcine retinal arterioles. The autoregulation pressure range for control and elevated levels of IOP is predicted. Results. The factor by which flow changes as the blood pressure exiting the central retinal artery is varied between 28 and 40 mm Hg is used to indicate the degree of autoregulation (1 indicates perfect autoregulation). In the presence of only the myogenic response mechanism, the factor is 2.06. In the presence of the myogenic and CO2 responses, the factor is 1.22. The combination of myogenic, shear, CO2, and metabolic responses yields the best autoregulation (factor of 1.10). Conclusions. Model results are compared with flow and pressure data from multiple patient studies, and the combined effects of the metabolic and CO2 responses are predicted to be critical for achieving retinal autoregulation. When IOP is elevated, the model predicts a decrease in the autoregulation range toward low perfusion pressure, which is consistent with observations that glaucoma is associated with decreased perfusion pressure.
The microcirculation plays a major role in maintaining homeostasis in the body. Alterations or dysfunctions of the microcirculation can lead to several types of serious diseases. It is not surprising, then, that the microcirculation has been an object of intense theoretical and experimental study over the past few decades. Mathematical approaches offer a valuable method for quantifying the relationships between various mechanical, hemodynamic, and regulatory factors of the microcirculation and the pathophysiology of numerous diseases. This work provides an overview of several mathematical models that describe and investigate the many different aspects of the microcirculation, including geometry of the vascular bed, blood flow in the vascular networks, solute transport and delivery to the surrounding tissue, and vessel wall mechanics under passive and active stimuli. Representing relevant phenomena across multiple spatial scales remains a major challenge in modeling the microcirculation. Nevertheless, the depth and breadth of mathematical modeling with applications in the microcirculation is demonstrated in this work. A special emphasis is placed on models of the retinal circulation, including models that predict the influence of ocular hemodynamic alterations with the progression of ocular diseases such as glaucoma.