The contribution of glycosaminoglycans to the mechanical behaviour of the posterior human sclera

Murienne, Barbara J.; Chen, Michelle L.; Quigley, Harry A.; Nguyen, Thao D.

doi:10.1098/rsif.2016.0367

Cited by 42 publications

(45 citation statements)

References 66 publications

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“…Enzymatic digestion of post mortem human ONH alters its biomechanical properties (Spoerl et al, 2005), and digestion with chondroitinase alters scleral strain in porcine globes in the opposite direction to that seen with GA treatment (Murienne et al, 2013). Investigations of experimental glaucoma both in monkeys (Burgoyne et al, 2005) and mice (Cone et al, 2010) suggest that both baseline scleral structure and its dynamic response to elevated IOP may be important determinants of glaucomatous damage.…”

Section: Discussionmentioning

confidence: 99%

Experimental scleral cross-linking increases glaucoma damage in a mouse model

Kimball

Nguyen

Steinhart

et al. 2014

Experimental Eye Research

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The purpose of this study was to assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model. CD1 mice underwent 3 subconjunctival injections of 0.5 M glyceraldehyde (GA) in 1 week, then had elevated intraocular pressure (IOP) induced by bead injection. Degree of cross-linking was measured by enzyme-linked immunosorbent assay (ELISA), scleral permeability was measured by fluorescence recovery after photobleaching (FRAP), and the mechanical effects of GA exposure were measured by inflation testing. Control mice had buffer injection or no injection in 2 separate glaucoma experiments. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable effects of GA, we performed electroretinography and detailed histology of the retina. GA exposure had no detectable effects on RGC number, retinal structure or function either histologically or electrophysiologically. GA increased cross-linking of sclera by 37% in an ELISA assay, decreased scleral permeability (FRAP, p = 0.001), and produced a steeper pressure—strain behavior by in vitro inflation testing. In two experimental glaucoma experiments, GA-treated eyes had greater RGC axon loss from elevated IOP than either buffer-injected or control eyes, controlling for level of IOP exposure over time (p = 0.01, and 0.049, multivariable regression analyses). This is the first report that experimental alteration of the sclera, by cross-linking, increases susceptibility to RGC damage in mice.

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Section: Discussionmentioning

confidence: 99%

Experimental scleral cross-linking increases glaucoma damage in a mouse model

Kimball

Nguyen

Steinhart

et al. 2014

Experimental Eye Research

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“…This suggests that a relation between sGAG content and mechanical response of the sclera might exist. In support of this hypothesis, recent experiments have shown that sGAGs had a significant effect on inflation mechanical behavior of sclera [24,25]. In particular, it was seen that sGAG removal led to an overall more compliant mechanical behavior of porcine sclera.…”

Section: Discussionmentioning

confidence: 71%

“…The mechanical function of sGAGs in tissues such as tendon [13][14][15][16][17], ligament [18,19], and articular cartilage [20][21][22] has been extensively examined; however, their possible effects on mechanical properties of scleral tissue have been less studied [23][24][25]. Furthermore, pressure-controlled inflation experiments showed that sGAG removal had different effects on human porcine samples, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, pressure-controlled inflation experiments showed that sGAG removal had different effects on human porcine samples, i.e. it decreased the stiffness of porcine posterior sclera while it increased the stiffness of human sclera [24,25]. This contradictory effects of sGAGs have been associated to the older age of human donor samples compared to the porcine ones.…”

Section: Introductionmentioning

confidence: 99%

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The contribution of sGAGs to stress-controlled tensile response of posterior porcine sclera

Hatami-Marbini

Pachenari

2020

PLoS ONE

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Despite the significant progress in characterizing mechanical functions of individual scleral extracellular matrix (ECM) components, the biomechanical contribution of sulfated glycosaminoglycans (sGAGs) is still poorly understood. The primary purpose of this study was to determine the possible function of sGAGs in scleral mechanical response by characterizing the tensile behavior of normal and sGAG-depleted samples. We used chondroitinase ABC solution to remove sGAGs from scleral samples that were dissected from posterior porcine eyes. We performed biochemical analyses for assessing the efficacy of sGAG removal protocol. Furthermore, we conducted stress-controlled uniaxial tensile tests to characterize the influence of sGAG removal on mechanical properties of sclera. The tensile behavior of scleral strips right after dissection and after being soaked in buffer was also determined. Biochemical analyses confirmed that 18 hour incubation in 0.125 U/ml Chondroitinase ABC solution removed over 90% of chondroitin and dermatan sGAGs. No significant difference was observed in the thickness/hydration of samples because of enzyme-and buffer-treated samples. Furthermore, it was found that sGAG depletion did not significantly alter the tangent modulus, energy dissipation, and peak strain of posterior scleral strips. It was concluded that sGAGs did not influence the stress-controlled viscoelastic tensile response of sclera. OPEN ACCESSCitation: Hatami-Marbini H, Pachenari M (2020) The contribution of sGAGs to stress-controlled tensile response of posterior porcine sclera. PLoS ONE 15(2): e0227856. https://doi.org/10.

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“…10,18,19 As such, depletion or misregulation of GAGs is often associated with natural aging 20 or debilitating diseases. [21][22][23] Notably, it has been proposed that misregulation of GAGs perturbs the mechanobiology of the ECM, leading to a loss of biological function and aberrant cell activity. 7 However, the mechanism and extent to which GAGs alter individual collagen fibrils has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Probing the effect of glycosaminoglycan depletion on integrin interactions with collagen I fibrils in the native ECM environment

Roth

Hoop

Williams

et al. 2020

Preprint

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Collagen fibrils serve as the molecular scaffolding for connective tissues throughout the human body and are the most abundant protein building block in the extracellular matrix (ECM). Glycosaminoglycans (GAGs) are an important class of polysaccharides in the ECM that mediate collagen fibril development, cell adhesion and motility, wound healing, inter alia. Depletion or mis-regulation of GAGs has been shown to be intimately related to diseases such as cancer, hyperglycemia, and glaucoma. However, the molecular-level coordination between collagen fibrils and GAGs to regulate ECM mechanobiology is unclear. Here, high resolution atomic force microscopy experiments are used to assess perturbations to nanoscale topography and mechanical properties of single collagen fibrils upon GAG depletion in aqueous solution. Fast force maps show that GAG depletion lowers indentation modulus by about half compared to native fibrils while retaining a key structural motif (D-banding). These results shed new light on the functional role of GAGs and may aid in strategies to treat diseases that impair ECM mechanobiology.

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The contribution of glycosaminoglycans to the mechanical behaviour of the posterior human sclera

Cited by 42 publications

References 66 publications

Experimental scleral cross-linking increases glaucoma damage in a mouse model

Experimental scleral cross-linking increases glaucoma damage in a mouse model

The contribution of sGAGs to stress-controlled tensile response of posterior porcine sclera

Probing the effect of glycosaminoglycan depletion on integrin interactions with collagen I fibrils in the native ECM environment

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