The Role of the Eye's Peri-limbal Tissue and Integral Veins on Intraocular Pressure

角膜外缘周围的眼组织（角膜缘周围巩膜组织）的机械特性包含静脉，其允许从眼睛内部的透明胶状物（房水）引流。角膜缘周围组织是眼睛用来控制眼压的机制的一部分。 这项研究将测试角膜缘周围组织的机械特性是否会改变静脉控制眼压的方式。研究目标是：（1）测量流出发生时支撑静脉的组织中的变形;（2）确定角膜缘周围组织机械特性和变形与眼睛的眼内压之间的关系;（3）确定角膜缘周围巩膜组织影响静脉从眼睛运送流体的能力的机械机制。将通过显微镜成像的变形角膜缘周围巩膜的实验灌注下追求的目标。注入眼睛的人工水溶液中的荧光纳米球将产生可跟踪的标记，用于测量变形。 基于实验数据，建立了角膜缘周围巩膜及其静脉的微观结构解剖的流体-结构相互作用的计算机模型。 眼压升高通常与青光眼有关，影响40岁以上人口的约10%，使其成为不可逆失明的主要原因之一。这项研究将通过发现青光眼眼压升高的一些基本原因来促进公共卫生。 在此基础上，将为主要研究者的软组织课程开发顶点设计项目和教育模块。超过六名学生将在这个跨学科的项目，以及两个本科生为该项目的每一年工作。 这些学生将来自密歇根大学两个校区和邻近机构的工程、自然科学和医学专业，以扩大该项目的影响。成像将在眼睛组织内进行，而不是在表面。这将产生关于静脉和周围软组织的相互作用以及眼内压通过巩膜转移到静脉的新知识。除了了解水静脉系统产生背压之外，对其结构细节和流出之间的关系知之甚少;这些知识将在本项目中得到发展。知识也将导致粘弹性组织特性、应变和眼压之间的关系。这种知识与具有高压的眼睛中的青光眼直接相关。此外，由于粘弹性组织特性与细胞外基质的组分及其重塑密切相关，因此将出现适用于衰老和组织疾病的知识。在正常角膜缘周围巩膜中产生的技术和知识可以应用于糖尿病组织，以更好地理解具有晚期糖基化终产物的组织中生物力学和变形的差异，晚期糖基化终产物是组织硬化的疑似原因。所使用的方法和获得的知识将有助于了解身体的其他组织，其中软组织和液体输送血管相互作用，如肾小管，脑静脉和视网膜静脉。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The mechanical properties of the eye tissues around the outer rim of the cornea (peri-limbal scleral tissue) contains veins that allow drainage from the clear jelly (aqueous humor) of the inside of the eye. The peri-limbal tissues are part of the mechanism that the eye uses to control eye pressure. This research will test whether the mechanical properties of the peri-limbal tissues changes how the veins control eye pressure. The research goals are to: (1) measure the deformation in the tissues supporting the veins as outflow occurs; (2) determine the relationships between peri-limbal tissue mechanical properties and deformation with the eye's intraocular pressure; (3) determine the mechanical mechanisms by which the peri-limbal scleral tissues influence the veins' ability to carry fluid from the eye. The objectives will be pursued through microscopic imaging of the deforming peri-limbal sclera of eyes under experimental perfusion. Fluorescent nanospheres in artificial aqueous infused into the eye will create trackable markers that will be used to measure deformation. A computer model of the fluid-structure interaction based on the experimental data will be created for the microstructural anatomy of the peri-limbal sclera and the included veins. Elevated eye pressure is often implicated in glaucoma and affects about 10% of the population over age 40, making it one of the leading causes of irreversible blindness. This research will further public health by discovering some of the basic causes of eye pressure increase in glaucoma. Capstone design projects and educational module for the principal investigators soft tissue class will be developed based on the research. More than six students will work on this interdisciplinary project, as well as two undergraduates for each year of the project. These students will come from engineering, natural science and medicine on the two University of Michigan campuses and neighboring institutions to expand the project's impact.The imaging will be conducted within the eye's tissues, not on the surface. This will produce new knowledge about the interaction of veins and the surrounding soft tissue as well as the transfer of intraocular pressure through the sclera and to the veins. Other than understanding that the aqueous venous system creates a back-pressure, little is known about the relationship between its structural details and outflow; such knowledge will be developed in this project. Knowledge will also result on the relationships between the viscoelastic tissue properties, strains and eye pressure. This knowledge has direct relevance to glaucoma in eyes having high pressure. Furthermore, because the viscoelastic tissue properties are strongly tied to components of the extracellular matrix and its remodeling, knowledge will occur that has application to aging and tissue disorders. The techniques and knowledge produced in normal peri-limbal sclera can be applied to diabetic tissues to better understand the differences in biomechanics and deformation in tissues with advanced glycation end products, a suspected cause of tissue stiffening. The methods used and knowledge gained will inform understanding of other tissues of the body where soft tissue and fluid acconveying vessels interact such as the renal tubules, cerebral veins, and retinal veins.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.