☆ 4.4 Review

Glaucoma and biomechanics

CURRENT OPINION IN OPHTHALMOLOGY (2022)

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Summary: Over the past two decades, quantitative mapping of deformation and elasticity in optical coherence tomography has been a focus of research, and it took about 15 years to demonstrate optical coherence elastography as a useful technique. Compression OCE and shear-wave-based OCE have developed in parallel, with recent breakthroughs in quantitative mapping in Compression OCE but insufficient attention in reviews.

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Adduction-Induced Strain on the Optic Nerve in Primary Open Angle Glaucoma at Normal Intraocular Pressure

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Summary: The study found that in healthy individuals, the optic nerve stretches to absorb force and prevent globe retraction during adduction, while in POAG patients, the relatively inelastic optic nerve tethers and retracts the globe during adduction beyond 26 degrees, potentially leading to progressive neuropathy.

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Summary: Intraocular pressure (IOP) fluctuates due to ocular pulse, which induces shear stress in Schlemm's canal (SC). The ocular pulse may modulate outflow facility by stimulating NO production. Studies showed the immediate increase in outflow facility in mice in response to the ocular pulse, with NO playing a significant role in this regulation.

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In vivo estimation of murine iris stiffness using finite element modeling

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Summary: The study aimed to estimate the murine iris biomechanical stiffness by utilizing optical coherence tomography images for living mice and an inverse finite element model. The in vivo murine iris stiffness was found to be 96.1 +/- 54.7 kPa, with gender dependency and evidence of reverse pupillary block. The approach of monitoring iris stiffness in vivo has significant potential for studying potential changes in various pathophysiological conditions of the iris.

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Summary: The study investigated nuclear shape alterations in iris tissue, finding an increase in nuclear aspect ratio after inducing iris deformation through activation of smooth muscles. The findings suggest the potential for using 3D reconstructions in future computational models to study primary angle-closure glaucoma, as they provide more physiologically realistic values compared to 2D projected images. Moreover, the study indicates that iris stromal cells are subjected to a biomechanically active micro-environment during their physiological function in response to ambient light.

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Individual-Specific Modeling of Rat Optic Nerve Head Biomechanics in Glaucoma

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Summary: Glaucoma is characterized by the death of retinal ganglion cells (RGCs) due to elevated intraocular pressure (IOP), but the precise mechanism of how biomechanical insult leads to RGC death is not fully understood. This study utilized finite element modeling to analyze the biomechanics of rat optic nerve heads (ONHs) and found that changing the collagen fiber direction to be circumferential within the peripapillary sclera resulted in more pronounced decreases in strain than changing scleral stiffness. The results from this study can provide insight into how biomechanics affects RGC pathogenesis in glaucoma.

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Summary: The trabecular meshwork is a highly mechanosensitive tissue in the eye that regulates intraocular pressure. This study identified the Piezo1 channel as a key transducer of mechanical stimuli in TM cells, shedding light on the mechanisms of intraocular pressure regulation.

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The Canonical Wnt Signaling Pathway Inhibits the Glucocorticoid Receptor Signaling Pathway in the Trabecular Meshwork

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Changes in Corneal Biomechanics and Glaucomatous Visual Field Loss

Eric Chan et al.

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Summary: The study utilized an ultrasonic elastography system to investigate the biomechanical properties of porcine eyes under different intraocular pressures. The results showed an increase in Young's modulus of both optic nerve head and peripapillary sclera with increasing intraocular pressure, while they tended to become stiffer with decreasing intraocular pressure.

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TRPV4-Rho signaling drives cytoskeletal and focal adhesion remodeling in trabecular meshwork cells

Monika Lakk et al.

Summary: In this study, it was found that mechanical stretch promoted F-actin polymerization, increased the number and size of focal adhesions, and stimulated the activation of the Rho-associated protein kinase (ROCK) in human TM cells. The activation of both TRPV4 and ROCK were required for zyxin translocation and an increase in the number/size of focal adhesions in stretched cells. These results reveal the complex signaling pathways involved in the mechanical tuning of TM cells.

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Transpupillary collagen photocrosslinking for targeted modulation of ocular biomechanics

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Summary: This study aimed to reduce tissue deformation near the optic nerve head by selectively stiffening the peripapillary sclera, and successfully demonstrated a targeted photocrosslinking approach that may be beneficial in future glaucoma treatments. While this method effectively stiffened the sclera, there were some ocular toxicities associated with photocrosslinking.

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A tissue-engineered human trabecular meshwork hydrogel for advanced glaucoma disease modeling

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Iridocorneal contact as a potential cause of corneal decompensation following laser peripheral iridotomy

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Summary: This study found that corneal endothelial cell density may decrease after LPI due to mechanical damage from iridocorneal endothelial contact.

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Corneal Biomechanical Changes Caused by Acute Elevation of IOP in Eyes with and without Glaucoma

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Summary: Although acute elevation of intraocular pressure resulted in significant changes in corneal hysteresis and corneal resistance factor, these changes do not seem to have a prognostic value for glaucoma or its progression.

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Primary cilia and the reciprocal activation of AKT and SMAD2/3 regulate stretch-induced autophagy in trabecular meshwork cells

Myoung Sup Shim et al.

Summary: This study identified primary cilia as the mechanosensor for cyclic mechanical stretch-induced autophagy in trabecular meshwork cells. The cross-regulation between AKT1 and noncanonical SMAD2/3 signaling was found to be critical in primary cilia-mediated activation of autophagy by mechanical stretch. Removal of primary cilia disrupted the homeostatic intraocular pressure compensatory response, highlighting the importance of primary cilia-mediated autophagy in regulating intraocular pressure homeostasis.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Impaired TRPV4-eNOS signaling in trabecular meshwork elevates intraocular pressure in glaucoma

Pinkal D. Patel et al.

Summary: TRPV4 channels play a crucial role in regulating intraocular pressure and can be activated by increased fluid flow. Impaired TRPV4 channel activity in glaucomatous patients contributes to elevated intraocular pressure, highlighting the importance of TRPV4-eNOS signaling in IOP regulation.

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Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis

Guorong Li et al.

Summary: Netarsudil reduces glucocorticoid-induced ocular hypertension by preventing or attenuating pathologies, acting directly on conventional outflow cells. These findings warrant a randomized prospective clinical study to evaluate its superiority in lowering steroid-induced ocular hypertension.

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Summary: ONH biomechanics plays a central role in glaucoma pathogenesis. By conducting micromechanical testing and finite element modeling on porcine ONH tissue samples, this study provided detailed descriptions of ONH viscoelastic properties and identified a dual mechanism of fluid flow and solid matrix viscoelasticity in the mechanical response of ONH. The obtained properties can be utilized for designing ex vivo test environments and understanding glaucoma pathophysiology.

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Hamed Hatami-Marbini et al.

Summary: This study investigates the structural roles of GAGs in the scleral tensile properties and found that removal of GAGs results in stiffer tensile behavior, independent of displacement rate. Preconditioning does not significantly affect the tensile behavior of GAG depleted and normal scleral strips.

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The vital role for nitric oxide in intraocular pressure homeostasis

Ester Reina-Torres et al.

Summary: Nitric oxide, catalyzed by endothelial nitric oxide synthase (eNOS) activity, plays a crucial role in maintaining endothelial and cardiovascular homeostasis. In the conventional outflow pathway of the eye, NO is a key player in regulating aqueous humor outflow resistance.

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Jiyoung Lee et al.

Summary: The study revealed that MCP-1 and IL-8 can induce the formation of actin stress fibers and focal adhesions in TM cells, promote myosin light chain phosphorylation and cell contraction. Additionally, these chemokines also elevate the levels of extracellular matrix proteins and enhance cell migration, leading to increased resistance to aqueous outflow in viral anterior uveitis and POAG.

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RhoA/ROCK-YAP/TAZ Axis Regulates the Fibrotic Activity in Dexamethasone-Treated Human Trabecular Meshwork Cells

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Summary: High intraocular pressure is a major risk factor for glaucoma, and abnormal fibrotic activity in human trabecular meshwork cells is considered responsible for increased resistance to aqueous humor outflow. This study used bioinformatics to identify fibrotic pathways in DEX-treated HTM cells, revealing the crucial role of RhoA/ROCK-YAP/TAZ axis in regulating fibrotic activity.

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Regional Differences and Physiologic Behaviors in Peripapillary Scleral Fibroblasts

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Masato Matsuura et al.

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Wnt Activation After Inhibition Restores Trabecular Meshwork Cells Toward a Normal Phenotype

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JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME (2015)

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Review Ophthalmology

Translating Ocular Biomechanics into Clinical Practice: Current State and Future Prospects

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CURRENT EYE RESEARCH (2015)

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Article Engineering, Biomedical

An inverse method to determine the mechanical properties of the iris in vivo

Kunya Zhang et al.

BIOMEDICAL ENGINEERING ONLINE (2014)

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Article Ophthalmology

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

Elizabeth C. Kimball et al.

EXPERIMENTAL EYE RESEARCH (2014)

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Article Biophysics

Biomechanics of the Posterior Eye: A Critical Role in Health and Disease

Ian C. Campbell et al.

JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME (2014)

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Review Cell Biology

Development of diagnostic and treatment strategies for glaucoma through understanding and modification of scleral and lamina cribrosa connective tissue

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CELL AND TISSUE RESEARCH (2013)

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Article Pharmacology & Pharmacy

Immune regulation toward immunomodulation for neuroprotection in glaucoma

Guelguen Tezel

CURRENT OPINION IN PHARMACOLOGY (2013)

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Article Ophthalmology

Estimation of Ocular Rigidity in Glaucoma Using Ocular Pulse Amplitude and Pulsatile Choroidal Blood Flow

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INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2013)

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Article Ophthalmology

Correlation Between Biomechanical Responses of Posterior Sclera and IOP Elevations During Micro Intraocular Volume Change

Hugh J. Morris et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2013)

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Article Ophthalmology

Studies of Scleral Biomechanical Behavior Related to Susceptibility for Retinal Ganglion Cell Loss in Experimental Mouse Glaucoma

Cathy Nguyen et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2013)

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Review Ophthalmology

Angle closure and angle-closure glaucoma: what we are doing now and what we will be doing in the future

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CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY (2012)

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Proteomics Analyses of Human Optic Nerve Head Astrocytes Following Biomechanical Strain

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MOLECULAR & CELLULAR PROTEOMICS (2012)

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Lamina cribrosa thickening in early glaucoma predicted by a microstructure motivated growth and remodeling approach

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MECHANICS OF MATERIALS (2012)

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Perspectives on biomechanical growth and remodeling mechanisms in glaucoma

Rafael Grytz et al.

MECHANICS RESEARCH COMMUNICATIONS (2012)

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Article Ophthalmology

Proteomics Analyses of Activated Human Optic Nerve Head Lamina Cribrosa Cells following Biomechanical Strain

Ronan Rogers et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2012)

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Article Ophthalmology

Quantitative Mapping of Collagen Fiber Orientation in Non-glaucoma and Glaucoma Posterior Human Sclerae

Jacek K. Pijanka et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2012)

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Article Ophthalmology

Biomechanics of the Human Posterior Sclera: Age- and Glaucoma-Related Changes Measured Using Inflation Testing

Baptiste Coudrillier et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2012)

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Article Biophysics

The collagen fibril architecture in the lamina cribrosa and peripapillary sclera predicted by a computational remodeling approach

Rafael Grytz et al.

BIOMECHANICS AND MODELING IN MECHANOBIOLOGY (2011)

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Article Ophthalmology

Increased iris thickness and association with primary angle closure glaucoma

B-S Wang et al.

BRITISH JOURNAL OF OPHTHALMOLOGY (2011)

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Article Ophthalmology

Finite element modeling of the human sclera: Influence on optic nerve head biomechanics and connections with glaucoma

Richard E. Norman et al.

EXPERIMENTAL EYE RESEARCH (2011)

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Article Ophthalmology

Elastic Modulus Determination of Normal and Glaucomatous Human Trabecular Meshwork

Julie A. Last et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2011)

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Article Ophthalmology

Microstructural Differences in the Human Posterior Sclera as a Function of Age and Race

Dongmei Yan et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2011)

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Article Engineering, Biomedical

Effects of Scleral Stiffness Properties on Optic Nerve Head Biomechanics

Armin Eilaghi et al.

ANNALS OF BIOMEDICAL ENGINEERING (2010)

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Article Ophthalmology

Dimensions of the human sclera: Thickness measurement and regional changes with axial length

Richard E. Norman et al.

EXPERIMENTAL EYE RESEARCH (2010)

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Review Ophthalmology

Biomechanics of the optic nerve head

Ian A. Sigal et al.

EXPERIMENTAL EYE RESEARCH (2009)

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Mitochondrial Dysfunction and Glaucoma

George Y. X. Kong et al.

JOURNAL OF GLAUCOMA (2009)

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Article Ophthalmology

Iris Cross-sectional Area Decreases With Pupil Dilation and its Dynamic Behavior is a Risk Factor in Angle Closure

Harry A. Quigley et al.

JOURNAL OF GLAUCOMA (2009)

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Article Biophysics

VASCULAR MECHANICS, MECHANOBIOLOGY, AND REMODELING

J. D. Humphrey

JOURNAL OF MECHANICS IN MEDICINE AND BIOLOGY (2009)

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Review Ophthalmology

Premise and prediction - How optic nerve head biomechanics underlies the susceptibility and clinical behavior of the aged optic nerve head

Claude F. Burgoyne et al.

JOURNAL OF GLAUCOMA (2008)

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Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma

John P. Berdahl et al.

OPHTHALMOLOGY (2008)

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Article Ophthalmology

Predicted extension, compression and shearing of optic nerve head tissues

Ian A. Sigal et al.

EXPERIMENTAL EYE RESEARCH (2007)

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Article Ophthalmology

Connective tissue structure of the tree shrew optic nerve and associated ageing changes

Julie Albon et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2007)

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Article Pathology

Mechanobiology of bone tissue

J Klein-Nulend et al.

PATHOLOGIE BIOLOGIE (2005)

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Article Ophthalmology

Factors influencing optic nerve head biomechanics

IA Sigal et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2005)

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Review Ophthalmology

The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage

CF Burgoyne et al.

PROGRESS IN RETINAL AND EYE RESEARCH (2005)

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Article Ophthalmology

Effect of cyclical mechanical stretch and exogenous transforming growth factor-β1 on matrix metalloproteinase-2 activity in lamina cribrosa cells from the human optic nerve head

RP Kirwan et al.

JOURNAL OF GLAUCOMA (2004)

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Article Ophthalmology

Finite element modeling of optic nerve head biomechanics

IA Sigal et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2004)

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Article Ophthalmology

Reduction of intraocular pressure and glaucoma progression - Results from the early manifest glaucoma trial

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ARCHIVES OF OPHTHALMOLOGY (2002)

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