Murienne Barbara J, Jefferys Joan L, Quigley Harry A, Nguyen Thao D
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Glaucoma Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Acta Biomater. 2015 Jan;12:195-206. doi: 10.1016/j.actbio.2014.10.033. Epub 2014 Nov 4.
Pathological changes in scleral glycosaminoglycan (GAG) content and in scleral mechanical properties have been observed in eyes with glaucoma and myopia. The purpose of this study is to investigate the effect of GAG removal on the scleral mechanical properties to better understand the impact of GAG content variations in the pathophysiology of glaucoma and myopia. We measured how the removal of sulphated GAG (s-GAG) affected the hydration, thickness and mechanical properties of the posterior sclera in enucleated eyes of 6-9 month-old pigs. Measurements were made in 4 regions centered on the optic nerve head (ONH) and evaluated under 3 conditions: no treatment (control), after treatment in buffer solution alone, and after treatment in buffer containing chondroitinase ABC (ChABC) to remove s-GAGs. The specimens were mechanically tested by pressure-controlled inflation with full-field deformation mapping using digital image correlation (DIC). The mechanical outcomes described the tissue tensile and viscoelastic behavior. Treatment with buffer alone increased the hydration of the posterior sclera compared to controls, while s-GAG removal caused a further increase in hydration compared to buffer-treated scleras. Buffer-treatment significantly changed the scleral mechanical behavior compared to the control condition, in a manner consistent with an increase in hydration. Specifically, buffer-treatment led to an increase in low-pressure stiffness, hysteresis, and creep rate, and a decrease in high-pressure stiffness. ChABC-treatment on buffer-treated scleras had opposite mechanical effects than buffer-treatment on controls, leading to a decrease in low-pressure stiffness, hysteresis, and creep rate, and an increase in high-pressure stiffness and transition strain. Furthermore, s-GAG digestion dramatically reduced the differences in the mechanical behavior among the 4 quadrants surrounding the ONH as well as the differences between the circumferential and meridional responses compared to the buffer-treated condition. These findings demonstrate a significant effect of s-GAGs on both the stiffness and time-dependent behavior of the sclera. Alterations in s-GAG content may contribute to the altered creep and stiffness of the sclera of myopic and glaucoma eyes.
在青光眼和近视眼中已观察到巩膜糖胺聚糖(GAG)含量及巩膜力学性能的病理变化。本研究的目的是探究去除GAG对巩膜力学性能的影响,以更好地理解GAG含量变化在青光眼和近视病理生理学中的作用。我们测量了去除硫酸化GAG(s - GAG)对6 - 9月龄猪摘除眼球后巩膜的水化、厚度及力学性能的影响。在以视神经乳头(ONH)为中心的4个区域进行测量,并在3种条件下进行评估:未处理(对照)、仅在缓冲溶液中处理后以及在含有软骨素酶ABC(ChABC)的缓冲溶液中处理以去除s - GAG后。通过使用数字图像相关(DIC)的全场变形映射进行压力控制充气对标本进行力学测试。力学结果描述了组织的拉伸和粘弹性行为。与对照组相比,仅用缓冲溶液处理可增加后巩膜的水化,而与缓冲溶液处理的巩膜相比,去除s - GAG导致水化进一步增加。与对照条件相比,缓冲溶液处理显著改变了巩膜的力学行为,其方式与水化增加一致。具体而言,缓冲溶液处理导致低压刚度、滞后和蠕变率增加,高压刚度降低。在缓冲溶液处理的巩膜上进行ChABC处理产生的力学效应与缓冲溶液处理对照组相反,导致低压刚度、滞后和蠕变率降低,高压刚度和转变应变增加。此外,与缓冲溶液处理的情况相比,s - GAG消化显著降低了ONH周围4个象限之间力学行为的差异以及周向和子午线响应之间的差异。这些发现表明s - GAG对巩膜的刚度和时间依赖性行为具有显著影响。s - GAG含量的改变可能导致近视和青光眼患者巩膜的蠕变和刚度改变。