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Abstract：
OBJECTIVE: Intraocular pressure (IOP) is determined by aqueous humor outflow resistance, which is a function of the combined resistance of Schlemm\'s canal (SC) endothelium and the trabecular meshwork (TM) and their interactions in the juxtacanalicular connective tissue (JCT) region. Aqueous outflow in the conventional outflow pathway results in pressure gradient across the TM, JCT, and SC inner wall, and induces mechanical stresses and strains that influence the geometry and homeostasis of the outflow system. The outflow resistance is affected by alteration in tissues\' geometry, so there is potential for active, two-way, fluid-structure interaction (FSI) coupling between the aqueous humor (fluid) and the TM, JCT, and SC inner wall (structure). However, our understanding of the biomechanical interactions of the aqueous humor with the outflow connective tissues and its contribution to the outflow resistance regulation is incomplete.
METHODS: In this study, a microstructural finite element (FE) model of a human eye TM, JCT, and SC inner wall was constructed from a segmented, high-resolution histologic 3D reconstruction of the human outflow system. Three different elastic moduli (0.004, 0.128, and 51.5 MPa based on prior reports) were assigned to the TM/JCT complex while the elastic modulus of the SC inner wall was kept constant at 0.00748 MPa. The hydraulic conductivity was programmed separately for the TM, JCT, and SC inner wall using a custom subroutine. Cable elements were embedded into the TM and JCT extracellular matrix to represent the directional stiffness imparted by anisotropic collagen fibril orientation. The resultant stresses and strains in the outflow system were calculated using fluid-structure interaction method.
RESULTS: The higher TM/JCT stiffness resulted in larger stresses, but smaller strains in the outflow connective tissues, and resulted in a 4- and 5-fold larger pressure drop across the SC inner wall, respectively, compared to the most compliant model. Funneling through µm-sized SC endothelial pores was evident in the models at lower tissue stiffness, but aqueous flow was more turbulent in models with higher TM/JCT stiffness.
CONCLUSIONS: The mechanical properties of the outflow tissues play a crucial role in the hydrodynamics of the aqueous humor in the conventional outflow system.
METHODS: In this study, a microstructural finite element (FE) model of a human eye TM, JCT, and SC inner wall was constructed from a segmented, high-resolution histologic 3D reconstruction of the human outflow system. Three different elastic moduli (0.004, 0.128, and 51.5 MPa based on prior reports) were assigned to the TM/JCT complex while the elastic modulus of the SC inner wall was kept constant at 0.00748 MPa. The hydraulic conductivity was programmed separately for the TM, JCT, and SC inner wall using a custom subroutine. Cable elements were embedded into the TM and JCT extracellular matrix to represent the directional stiffness imparted by anisotropic collagen fibril orientation. The resultant stresses and strains in the outflow system were calculated using fluid-structure interaction method.
RESULTS: The higher TM/JCT stiffness resulted in larger stresses, but smaller strains in the outflow connective tissues, and resulted in a 4- and 5-fold larger pressure drop across the SC inner wall, respectively, compared to the most compliant model. Funneling through µm-sized SC endothelial pores was evident in the models at lower tissue stiffness, but aqueous flow was more turbulent in models with higher TM/JCT stiffness.
CONCLUSIONS: The mechanical properties of the outflow tissues play a crucial role in the hydrodynamics of the aqueous humor in the conventional outflow system.
摘要：
目的：眼内压（IOP）由房水流出阻力确定，这是Schlemm管（SC）内皮和小梁网（TM）的联合阻力的函数，以及它们在结膜结缔组织（JCT）区域的相互作用。常规流出路径中的水流出导致跨TM的压力梯度，JCT,和SC内壁，并引起机械应力和应变，从而影响流出系统的几何形状和稳态。流出阻力受组织几何形状改变的影响，所以有可能活跃，双向,房水（流体）和TM之间的流体-结构相互作用（FSI）耦合，JCT,和SC内壁（结构）。然而,我们对房水与流出结缔组织的生物力学相互作用及其对流出阻力调节的贡献的理解是不完整的。
方法：在本研究中，人眼TM的微结构有限元(FE)模型，JCT,SC内壁由分段而成，人体流出系统的高分辨率组织学三维重建。将三种不同的弹性模量(基于先前的报道,0.004、0.128和51.5MPa)分配给TM/JCT复合体,而SC内壁的弹性模量保持恒定在0.00748MPa。TM的水力传导率单独编程，JCT,和SC内壁使用自定义子程序。将电缆元件嵌入TM和JCT细胞外基质中，以代表各向异性胶原纤维取向赋予的定向刚度。使用流体-结构相互作用方法计算了流出系统中的应力和应变。
结果：较高的TM/JCT刚度导致较大的应力，但是流出结缔组织中的应变较小，并导致SC内壁上的压降增加了4倍和5倍，分别,与最合规的模型相比。在较低组织硬度的模型中，通过µm大小的SC内皮孔的漏斗是明显的，但在TM/JCT刚度较高的模型中，水流更加湍流。
结论：流出组织的机械特性在常规流出系统中房水的流体动力学中起着至关重要的作用。
方法：在本研究中，人眼TM的微结构有限元(FE)模型，JCT,SC内壁由分段而成，人体流出系统的高分辨率组织学三维重建。将三种不同的弹性模量(基于先前的报道,0.004、0.128和51.5MPa)分配给TM/JCT复合体,而SC内壁的弹性模量保持恒定在0.00748MPa。TM的水力传导率单独编程，JCT,和SC内壁使用自定义子程序。将电缆元件嵌入TM和JCT细胞外基质中，以代表各向异性胶原纤维取向赋予的定向刚度。使用流体-结构相互作用方法计算了流出系统中的应力和应变。
结果：较高的TM/JCT刚度导致较大的应力，但是流出结缔组织中的应变较小，并导致SC内壁上的压降增加了4倍和5倍，分别,与最合规的模型相比。在较低组织硬度的模型中，通过µm大小的SC内皮孔的漏斗是明显的，但在TM/JCT刚度较高的模型中，水流更加湍流。
结论：流出组织的机械特性在常规流出系统中房水的流体动力学中起着至关重要的作用。
