title: The effects of glycosaminoglycan degradation on the mechanical behavior of the posterior porcine sclera.
abstract: 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.
authors.affiliation: Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA. Electronic address: bmurien1@jhu.edu.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Murienne
authors.affiliation: Glaucoma Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Joan L
authors.initials: JL
authors.lastname: Jefferys
authors.affiliation: Glaucoma Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Harry A
authors.initials: HA
authors.lastname: Quigley
authors.affiliation: Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Thao D
authors.initials: TD
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D006025:Glycosaminoglycans / Q000378:metabolism*; D012590:Sclera / Q000378:metabolism*; D013552:Swine; D014867:Water / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D014867:Water
keywords: Chondroitinase ABC; Glaucoma; Inflation; Myopia; Sclera