Investigating the Relationship Between the Structure and Mechanical Behavior of the Lamina Cribrosa

青光眼是由视网膜神经节细胞及其轴突在筛板中的进行性死亡引起的致盲性疾病。 筛板是视神经头中的有孔结缔组织结构，其在轴突离开眼睛时机械地支撑轴突。 青光眼是美国失明的主要原因，影响约300万美国人。尽管检测到青光眼损害的眼内压水平变化很大，但该疾病的发病率和严重程度与眼内压密切相关。 降低眼内压可以减缓轴突损失。治疗的有效性因患者而异，10%的青光眼患者最终失明。 PI假设视神经乳头内眼内压引起的变形导致轴突损伤。此外，筛板微观结构的区域变化导致更大的损伤区域。在本项目中，PI将测量压力诱导的应变和筛板的结构。 这些将用于创建筛板模型，以确定为什么某些区域表现出更多的变形和更高的应力水平。了解视神经乳头结构和变形之间的关系可能会导致识别新的结构生物标志物，用于使用非侵入性成像早期检测青光眼，并开发更有效的患者特异性治疗策略。轴突损伤导致成人青光眼永久性视力丧失，早期发现是保护视力的关键。 该项目还将通过为研究生，本科生和高中生提供研究机会，使工程教育受益，涉及最先进的实验和建模方法。研究的目的是调查解剖结构和显微结构特征导致应变和应力水平区域变化的程度。我们将应用最近开发的膨胀测试，它使用多光子成像和数字体积相关，以测量筛板和周围的视乳头周围巩膜的三维变形场。膨胀试验方法还可测量视神经头组织的解剖结构。我们将分析这些区域差异和眼睛之间的结构和应变测量的具体相关性。这些数据将被用来开发特定的微机械模型，以研究筛板的纤维网络微结构的变形运动学和视神经乳头组织的结构-性能关系。最后，实验的结果和低比例的微观力学模型将被用于开发视神经头和巩膜的样本特定的有限元模型，以系统地评估微观结构和解剖特征对应变和应力状态的空间变化的贡献。 这项工作将推进对视神经乳头生物力学的基本理解，并通过对眼睛特定LC解剖结构、微观结构、变形的计算建模和统计分析来阐明结构与材料行为之间的关系。

Glaucoma is a blinding disease caused by the progressive death of retinal ganglion cells and their axons in the lamina cribrosa. The lamina cribrosa is a fenestrated connective tissue structure in the optic nerve head that mechanically supports axons as they exit the eye. Glaucoma is the leading cause of blindness in the US, affecting an estimated 3 million Americans. The incidence and severity of the disease strongly correlate with the intraocular pressure, though the level of the intraocular pressure at which glaucoma damage is detected varies widely. Lowering the intraocular pressure can slow axon loss. The effectiveness of the treatment varies among patients and 10% of patients diagnosed with glaucoma eventually go blind. The PIs hypothesize that deformation caused by the intraocular pressure in the optic nerve head causes axonal damage. Moreover regional variations in the microstructure of the lamina cribrosa lead to regions of greater damage. In this project, the PIs will measure the pressure-induced strains and the structure of the lamina cribrosa. These will be used to create models of the lamina cribrosa to determine why certain regions exhibit more deformation and higher stress levels. Understanding the relationship between the optic nerve head structure and deformation may lead to the identification of new structural biomarkers for the early detection of glaucoma using non-invasive imaging and to the development of more effective patient-specific treatment strategies. Axon damage produces permanent vision loss in adult glaucoma and early detection is key to preserving vision. The project will also benefit engineering education by providing research opportunities to graduate, undergraduate and high school students that involves state of the art experimental and modeling methods. The objective of the research is to investigate the extent that anatomical structure and microstructural features lead to regional variations in the strain and stress levels. We will apply a recently developed inflation test, which uses multiphoton imaging and digital volume correlation, to measure the three-dimensional deformation field in the lamina cribrosa and surrounding peripapillary sclera. The inflation test method also yields measurements of the anatomical structure of the optic nerve head tissues. We will analyze these for regional differences and for eye-specific correlations between the structural and strain measurements. The data will be used to develop specimen-specific micromechanical models to study the deformation kinematics of the fibrous network microstructure of the lamina cribrosa and the structure-properties relationship of the optic nerve head tissue. Finally, the outcomes of the experiments and lower scale micromechanical models will be used to develop specimen- specific finite element models of the optic nerve head and sclera to systematically evaluate the contributions of microstructural and anatomic features to the spatial variations in the strain and stress state. The work will advance fundamental understanding of the biomechanics of the optic nerve head and elucidate the relationship between the structure and material behavior through computational modeling and statistical analysis of the eye-specific LC anatomical structure, microstructure, deformation.