Glycosaminoglycan contribution to the structure-mechanical properties of the posterior sclera

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Johns Hopkins University
The sclera is the white outer shell and main load-bearing tissue of the eye. It resists the intraocular pressure, therefore maintaining the shape of the eye, and protects the more fragile intraocular structures, such as the retina, from external forces. Alterations to the scleral mechanical properties can lead to the initiation and development of ocular pathologies such as myopia, often characterized by an axial elongation of the globe, or glaucoma, where the transmission of the visual information to the brain is impaired by a detrimental mechanical environment at the optic nerve head, at the back of the eye. While studies reported alterations in the mechanical properties of the posterior sclera of glaucomatous and myopic eyes, others measured alterations in the tissue microstructure, including the glycosaminoglycan (GAG) content. The contribution of collagen and elastin to the mechanical behavior of connective tissues is well known and consistent among tissues. However, the mechanical role of GAGs is tissue-dependent and has never been studied in the sclera. Therefore, this work aims to investigate the contributions of GAGs to the structure and mechanical properties of the posterior sclera, as well as their possible mechanical role in glaucoma and myopia. This work developed experimental and numerical approaches to measure the structural and mechanical effects of sulphated glycosaminoglycans (s-GAGs) digestion in the posterior sclera. A setup was first developed to compare the two-dimensional (2D) and three-dimensional (3D) versions of digital image correlation (DIC) for a membrane under inflation. Although 2D-DIC can be useful to evaluate the profile behavior of materials inflated under experimental conditions that discourage the use of a stereovision system, only 3D-DIC can capture the 3D heterogeneous anisotropic mechanical behavior of the sclera, and was therefore used in this work. A protocol for s-GAG digestion was then developed and the inflation response of posterior scleral shells from pig and human eyes was measured before and after s-GAG degradation using 3D-DIC displacement tracking. Structural parameters such as the scleral thickness and hydration were also measured. A methodology was then developed to evaluate the error and uncertainty in strains due to the 3D-DIC displacement error and uncertainty for posterior scleral shells under inflation. An inverse finite element method (FEM) was finally applied to specimen-specific meshes of the porcine scleral shells to determine the effect of s-GAG degradation on the properties of the matrix and collagen components of the posterior sclera. It was concluded from this work that despite their low content compared to other structural components, s-GAG play measurable roles in the structure and mechanical properties of the posterior sclera, mainly through their effects on hydration and their interactions with the collagen fibrils. Additionally, s-GAGs could be involved in the altered scleral mechanical properties measured in glaucoma and myopia.
Glycosaminoglycans, Sclera, Chondroitinase ABC, Inflation testing, Digital image correlation, Inverse finite element method, Glaucoma, Myopia