Mathematical Modeling of Ocular Mechanics, Circulation and Oxygenation and their Relation to Glaucoma

青光眼是一种视神经受损，导致进行性、不可逆转的视力丧失的疾病。青光眼是世界范围内第二大致盲原因，但其发病机制和治疗方法尚不完全清楚。青光眼主要与眼压升高有关，可通过干预措施降低眼压。矛盾的是，据观察，许多人在眼压相对较低的情况下会发展为青光眼，而许多人在眼压升高的情况下从不会发展为青光眼。眼球循环受损和青光眼之间的联系已经被发现，并有助于解释这一悖论。然而，目前尚不清楚血流变化是与青光眼相关的视网膜细胞死亡的原因还是结果。因此，本研究的目的是使用眼血流调节和组织灌流和氧合的数学模型来确定血流动力学改变是青光眼损害的原发病还是继发性损害。具体地说，血管调节机制受损和眼压升高对血流的影响将通过模型模拟进行比较。这些效应将与组织氧合的模型预测有关，以了解眼球循环受损是否导致细胞死亡，或者细胞死亡是否是循环受损的原因。这项研究的结果将有助于解释眼睛结构和血流的临床测量，并为青光眼的新治疗策略提供洞察力。获得模型解所需的非标准技术是数学研究的活跃领域，因此该项目将为医学和数学领域做出重大贡献。此外，在眼睛中进行研究特别重要，因为它是人体内唯一可以轻松和非侵入性地观察和测量血液流动和全身血管特征的环境，甚至可以低至很小的水平(毛细血管)。这些测量不仅确定了青光眼的风险指标，还确定了目前正在降低人类生活质量的许多系统性疾病的风险指标，包括糖尿病、高血压和动脉粥样硬化。通过将对人类生理学基本原理的理论解释和描述与实验和临床测量相结合，这项研究具有影响多种疾病的知识和治疗的独特潜力。

Glaucoma is a disease in which the optic nerve is damaged, leading to progressive, irreversible loss of vision. Glaucoma is the second leading cause of blindness worldwide and yet its pathogenesis and treatment are not fully understood. Glaucoma is primarily associated with elevated intraocular pressure and is treated with interventions that lower this pressure. Paradoxically, it has been observed that many people develop glaucoma despite relatively low intraocular pressure and that many people never develop glaucoma despite elevated intraocular pressure. A link between impaired ocular circulation and glaucoma has been identified and helps to explain this paradox. It is unclear, however, if alterations in blood flow are a cause or effect of the retinal cell death associated with glaucoma. Therefore, the objective of this study is to use a mathematical model of ocular blood flow regulation and tissue perfusion and oxygenation to determine whether hemodynamic alterations are primary or secondary to glaucomatous damage. Specifically, the effects of impaired vascular regulation mechanisms and elevated intraocular pressure on blood flow will be compared using model simulations. These effects will be related to model predictions of tissue oxygenation in order to understand whether impaired ocular circulation causes cell death or if cell death is the cause of impaired circulation.The results of this study will aid the interpretation of clinical measurements of eye structure and blood flow and provide insight for new treatment strategies for glaucoma. The non-standard techniques required to obtain model solutions are active areas of research in mathematics, and thus this project will provide significant contributions to both medical and mathematical fields. Moreover, conducting studies in the eye is of particular importance because it is the only environment in the human body where blood flow and systemic vascular features can be observed and measured easily and non-invasively down to a very small level (capillary vessels). These measurements identify risk indicators not only of glaucoma but also of many systemic diseases currently diminishing the quality of human life, including diabetes, hypertension and atherosclerosis. By combining theoretical interpretations and descriptions of underlying principles of human physiology with experimental and clinical measurements, this study has a unique potential to impact the knowledge and treatment of multiple diseases.