Collagen Structure and Mechanical Properties of the Human Sclera: Analysis for the Effects of Age

Coudrillier, Baptiste; Pijanka, Jacek K.; Jefferys, Joan L.; Sørensen, Thomas; Quigley, Harry A.; Boote, Craig; Nguyen, Thao D.

doi:10.1115/1.4029430

Cited by 101 publications

(96 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Raising the steady-state IOP effectively increased the stiffness of the entire corneoscleral shell, whereas chemical crosslinking treatment only alters a small region. This suggests that ubiquitous alterations in corneoscleral stiffness due to aging (Coudrillier et al, 2015; Coudrillier et al, 2012; Fazio et al, 2014) or race/genetics (Grytz et al, 2014) could have a much stronger impact on IOP spikes and glaucoma risk than localized treatment such as corneal or scleral crosslinking.…”

Section: Discussionmentioning

confidence: 99%

Corneoscleral stiffening increases IOP spike magnitudes during rapid microvolumetric change in the eye

Clayson

Pan

Pavlatos

et al. 2017

Experimental Eye Research

View full text Add to dashboard Cite

Factors governing the steady-state IOP have been extensively studied; however, the dynamic aspects of IOP are less understood. Clinical studies have suggested that intraocular pressure (IOP) fluctuation may be associated with glaucoma risk. This study aims to investigate how stiffening of corneoscleral biomechanical properties affects IOP spikes induced by rapid microvolumetric change. Porcine eyes (n = 25 in total) were subjected to volumetric infusions before and after external treatment of a circular area (11 mm diameter) in either the central cornea or posterior sclera. The treated area in the control group was immersed in phosphate-buffered saline (PBS) for 40 min, while the treated area of the chemical crosslinking group was immersed in 4% glutaraldehyde/PBS for 40 min. A subset of the sham-treated eyes was also subjected to volumetric infusions at a raised steady-state IOP. The magnitude of IOP spikes increased after localized chemical crosslinking of either the cornea (27.5% increase, p < 0.001) or the sclera (14.3% increase, p < 0.001) with corneal crosslinking having a stronger effect than scleral crosslinking (p = 0.018). We also observed that raising the steady-state IOP from 15 to 25 mmHg resulted in marked increase in IOP spike magnitudes by 63.9% (p < 0.001). These results suggested that an increased corneoscleral stiffness could significantly increase IOP spike magnitudes at the same volumetric change. Corneal stiffness appeared to have a strong impact on the IOP spike magnitude and may play a major role in regulating rapid volume-pressure dynamics. An increase in steady-state IOP also resulted in larger IOP fluctuations due to the increased “apparent” stiffness of the ocular shell, suggesting a potential interaction between the magnitude of IOP and its fluctuations. Corneoscleral properties may represent additional pathways for understanding and managing glaucoma risk and warrant future investigation.

show abstract

Section: Discussionmentioning

confidence: 99%

Corneoscleral stiffening increases IOP spike magnitudes during rapid microvolumetric change in the eye

Clayson

Pan

Pavlatos

et al. 2017

Experimental Eye Research

View full text Add to dashboard Cite

show abstract

“…While these concepts remain central to the discussion of ONH biomechanics in general, and the pathophysiology of glaucomatous damage to the ONH tissues specifically, a large group of investigators have expanded our understanding of glaucoma through the application of biomechanics and mechanobiology to the cornea (He and Liu, 2009, 2011; Liu and He, 2009; Liu and Roberts, 2005), trabecular meshwork (Braakman et al, 2014; Li et al, 2012; Overby et al, 2009; Stamer et al, 2014; Thomasy et al, 2012; Zhou et al, 2012), sclera (Coudrillier et al, 2013; Coudrillier et al, 2015a, b; Coudrillier et al, 2015c; Dastiridou et al, 2013; Fazio et al, 2014a; Fazio et al, 2014b; Girard et al, 2011b; Grytz et al, 2014; Nguyen and Ethier, 2015; Pijanka et al, 2012; Quigley et al, 2015) and ONH (Clark, 2012; Downs, 2015; Eilaghi et al, 2010; Girard et al, 2016; Girard et al, 2011a; Girard et al, 2013; Grytz et al, 2012a; Lei et al, 2011; Sigal et al, 2012; Sigal and Ethier, 2009; Sigal et al, 2005b, 2009a, b; Sigal and Grimm, 2012; Sigal et al, 2014; Stewart et al, 2014; Wang et al, 2016; Zhang et al, 2015) in health and disease. In sections 2.2 through 2.10, the details of these concepts are reviewed.…”

Section: 0 Onh Anatomy and Biomechanics (Figures 1 – 12)mentioning

confidence: 99%

“…Computational models suggest that scleral stiffness (Sigal et al, 2011) and scleral collagen fiber organization (Girard et al, 2009b; Grytz et al, 2011) dictate the IOP-induced deformation exhibited by the ONH. Interestingly, the sclera exhibits significant biomechanical changes with age (Coudrillier et al, 2015a, b; Fazio et al, 2014a; Fazio et al, 2014b; Girard et al, 2009c), ethnicity (Fazio et al, 2014b), and following exposure to chronic IOP elevation (Coudrillier et al, 2015c; Downs et al, 2005; Girard et al, 2011b), both of which being major risk factors in human glaucoma.…”

Section: 0 Experimental Evidence Of Onh Connective Tissue Deformatimentioning

confidence: 99%

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications

Yang

Reynaud

Lockwood

et al. 2017

Progress in Retinal and Eye Research

View full text Add to dashboard Cite

In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model. In it we propose that the defining pathophysiology of a glaucomatous optic neuropathy involves deformation, remodeling, and mechanical failure of the ONH connective tissues. We view this as an active process, driven by astrocyte, microglial, fibroblast and oligodendrocyte mechanobiology. These cells, and the connective tissue phenomena they propagate, have primary and secondary effects on retinal ganglion cell (RGC) axon and laminar beam and retrolaminar capillary homeostasis that may initially be “protective” but eventually lead to RGC axonal injury, repair and/or cell death. The primary goal of this report is to summarize our 3D histomorphometric and optical coherence tomography (OCT)-based evidence for the early onset and progression of ONH connective tissue deformation and remodeling in monkey EG. A second goal is to explain the importance of including ONH connective tissue processes in characterizing the phenotype of a glaucomatous optic neuropathy in all species. A third goal is to summarize our current efforts to move from ONH morphology to the cell biology of connective tissue remodeling and axonal insult early in the disease. A final goal is to facilitate the translation of our findings and ideas into neuroprotective interventions that target these ONH phenomena for therapeutic effect.

show abstract

“…Murienne et al, (2014) measured significant changes in the inflation response of porcine sclera with removal of sulfated glycosaminoglycans by chondroitinase. Coudrillier et al, (2015, 2014, 2013, 2012) measured the inflation response of the human sclera and compared for the effects of age and glaucoma damage, and diabetes. The inflation response in all regions of the sclera stiffened significantly with age in the range of 40–90 years old (Coudrillier et al, 2012).…”

Section: Experimental Measurements Of Tissue Deformationmentioning

confidence: 99%

Biomechanical assessment in models of glaucomatous optic neuropathy

Nguyen

Ethier

2015

Experimental Eye Research

Self Cite

View full text Add to dashboard Cite

The biomechanical environment within the eye is of interest in both the regulation of intraocular pressure and the loss of retinal ganglion cell axons in glaucomatous optic neuropathy. Unfortunately, this environment is complex and difficult to determine. Here we provide a brief introduction to basic concepts of mechanics (stress, strain, constitutive relationships) as applied to the eye, and then describe a variety of experimental and computational approaches used to study ocular biomechanics. These include finite element modeling, direct experimental measurements of tissue displacements using optical and other techniques, direct experimental measurement of tissue microstructure, and combinations thereof. Thanks to notable technical and conceptual advances in all of these areas, we are slowly gaining a better understanding of how tissue biomechanical properties in both the anterior and posterior segments may influence the development of, and risk for, glaucomatous optic neuropathy. Although many challenging research questions remain unanswered, the potential of this body of work is exciting; projects underway include the coupling of clinical imaging with biomechanical modeling to create new diagnostic tools, development of IOP control strategies based on improved understanding the mechanobiology of the outflow tract, and attempts to develop novel biomechanically-based therapeutic strategies for preservation of vision in glaucoma.

show abstract

Collagen Structure and Mechanical Properties of the Human Sclera: Analysis for the Effects of Age

Cited by 101 publications

References 62 publications

Corneoscleral stiffening increases IOP spike magnitudes during rapid microvolumetric change in the eye

Corneoscleral stiffening increases IOP spike magnitudes during rapid microvolumetric change in the eye

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications

Biomechanical assessment in models of glaucomatous optic neuropathy

Contact Info

Product

Resources

About