Abstract：
OBJECTIVE: Intraocular pressure (IOP) is maintained via a dynamic balance between the production of aqueous humor and its drainage through the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm\'s canal (SC) endothelium of the conventional outflow pathway. Primary open angle glaucoma (POAG) is often associated with IOP elevation that occurs due to an abnormally high outflow resistance across the outflow pathway. Outflow tissues are viscoelastic and actively interact with aqueous humor dynamics through a two-way fluid-structure interaction coupling. While glaucoma affects the morphology and stiffness of the outflow tissues, their biomechanics and hydrodynamics in glaucoma eyes remain largely unknown. This research aims to develop an image-to-model method allowing the biomechanics and hydrodynamics of the conventional aqueous outflow pathway to be studied.
METHODS: We used a combination of X-ray computed tomography and scanning electron microscopy to reconstruct high-fidelity, eye-specific, 3D microstructural finite element models of the healthy and glaucoma outflow tissues in cellularized and decellularized conditions. The viscoelastic TM/JCT/SC complex finite element models with embedded viscoelastic beam elements were subjected to a physiological IOP load boundary; the stresses/strains and the flow state were calculated using fluid-structure interaction and computational fluid dynamics.
RESULTS: Based on the resultant hydrodynamics parameters across the outflow pathway, the primary site of outflow resistance in healthy eyes was in the JCT and immediate vicinity of the SC inner wall, while the majority of the outflow resistance in the glaucoma eyes occurred in the TM. The TM and JCT in the glaucoma eyes showed 1.32-fold and 1.13-fold larger beam thickness and smaller trabecular space size (2.24-fold and 1.50-fold) compared to the healthy eyes.
CONCLUSIONS: Characterizing the accurate morphology of the outflow tissues may significantly contribute to constructing more accurate, robust, and reliable models, that can eventually help to better understand the dynamic IOP regulation, hydrodynamics of the aqueous humor, and outflow resistance dynamic in the human eyes. This model demonstrates proof of concept for determining changes to outflow resistance in healthy and glaucomatous tissues and thus may be utilized in larger cohorts of donor tissues where disease specificity, race, age, and gender of the eye donors may be accounted for.
METHODS: We used a combination of X-ray computed tomography and scanning electron microscopy to reconstruct high-fidelity, eye-specific, 3D microstructural finite element models of the healthy and glaucoma outflow tissues in cellularized and decellularized conditions. The viscoelastic TM/JCT/SC complex finite element models with embedded viscoelastic beam elements were subjected to a physiological IOP load boundary; the stresses/strains and the flow state were calculated using fluid-structure interaction and computational fluid dynamics.
RESULTS: Based on the resultant hydrodynamics parameters across the outflow pathway, the primary site of outflow resistance in healthy eyes was in the JCT and immediate vicinity of the SC inner wall, while the majority of the outflow resistance in the glaucoma eyes occurred in the TM. The TM and JCT in the glaucoma eyes showed 1.32-fold and 1.13-fold larger beam thickness and smaller trabecular space size (2.24-fold and 1.50-fold) compared to the healthy eyes.
CONCLUSIONS: Characterizing the accurate morphology of the outflow tissues may significantly contribute to constructing more accurate, robust, and reliable models, that can eventually help to better understand the dynamic IOP regulation, hydrodynamics of the aqueous humor, and outflow resistance dynamic in the human eyes. This model demonstrates proof of concept for determining changes to outflow resistance in healthy and glaucomatous tissues and thus may be utilized in larger cohorts of donor tissues where disease specificity, race, age, and gender of the eye donors may be accounted for.
摘要：
目的：眼内压（IOP）是通过房水的产生及其通过小梁网（TM）的引流之间的动态平衡来维持的，结膜结缔组织（JCT），和施莱姆氏管（SC）常规流出途径的内皮。原发性开角型青光眼（POAG）通常与IOP升高有关，这是由于跨流出途径的异常高的流出阻力而发生的。流出组织是粘弹性的，并通过双向流体-结构相互作用耦合与房水动力学主动相互作用。虽然青光眼影响流出组织的形态和硬度，他们的生物力学和流体动力学在青光眼的眼睛仍然很大程度上未知。这项研究旨在开发一种图像到模型的方法，从而可以研究常规房水流出途径的生物力学和流体动力学。
方法：我们使用了X射线计算机断层扫描和扫描电子显微镜的组合来重建高保真，眼睛特异性，在细胞化和脱细胞化条件下健康和青光眼流出组织的3D微结构有限元模型。具有嵌入式粘弹性梁单元的粘弹性TM/JCT/SC复杂有限元模型受到生理IOP载荷边界；使用流体-结构相互作用和计算流体动力学计算应力/应变和流动状态。
结果：基于整个流出路径的最终流体动力学参数，健康眼睛流出阻力的主要部位是在JCT和SC内壁附近，而青光眼眼中的大部分流出阻力发生在TM中。与健康眼相比，青光眼眼中的TM和JCT显示出1.32倍和1.13倍的光束厚度和较小的小梁空间大小（2.24倍和1.50倍）。
结论：表征流出组织的准确形态可能显著有助于构建更准确的，健壮,和可靠的模型，这最终可以帮助更好地理解动态IOP调节，房水的流体动力学，以及人眼动态的流出阻力。该模型证明了确定健康和青光眼组织中流出阻力变化的概念证明，因此可用于疾病特异性的较大供体组织队列。种族,年龄,和眼睛捐赠者的性别可以解释。
方法：我们使用了X射线计算机断层扫描和扫描电子显微镜的组合来重建高保真，眼睛特异性，在细胞化和脱细胞化条件下健康和青光眼流出组织的3D微结构有限元模型。具有嵌入式粘弹性梁单元的粘弹性TM/JCT/SC复杂有限元模型受到生理IOP载荷边界；使用流体-结构相互作用和计算流体动力学计算应力/应变和流动状态。
结果：基于整个流出路径的最终流体动力学参数，健康眼睛流出阻力的主要部位是在JCT和SC内壁附近，而青光眼眼中的大部分流出阻力发生在TM中。与健康眼相比，青光眼眼中的TM和JCT显示出1.32倍和1.13倍的光束厚度和较小的小梁空间大小（2.24倍和1.50倍）。
结论：表征流出组织的准确形态可能显著有助于构建更准确的，健壮,和可靠的模型，这最终可以帮助更好地理解动态IOP调节，房水的流体动力学，以及人眼动态的流出阻力。该模型证明了确定健康和青光眼组织中流出阻力变化的概念证明，因此可用于疾病特异性的较大供体组织队列。种族,年龄,和眼睛捐赠者的性别可以解释。
