Interactions Between Factors Influencing Optic Nerve Head Biomechanics

2007 ◽  
Author(s):  
Ian A. Sigal ◽  
John G. Flanagan ◽  
C. Ross Ethier
Keyword(s):  
Optic Nerve ◽  
Optic Nerve Head ◽  
Mechanical Response ◽  
Ganglion Cells ◽  
Cell Damage ◽  
Mechanical Strain ◽  
Lamina Cribrosa ◽  
Retinal Ganglion ◽  
The Finite Element Method ◽  
Primary Risk Factor

Glaucoma is the second most common cause of blindness worldwide, and elevated intraocular pressure (IOP) is the primary risk factor for developing this disease. It has been postulated that IOP-induced mechanical strain on optic nerve head (ONH) glial cells leads to retinal ganglion cell damage and the consequent loss of vision in glaucoma. To better evaluate this theory it is important to understand the biomechanical environment within the ONH. Unfortunately it is very difficult to make measurements in the ONH, and it is particularly difficult to access the region in the ONH where the ganglion cells are thought to be injured, namely the lamina cribrosa. We have therefore developed models of the ONH and used the finite element method (FEM) to predict ONH mechanical response to changes in IOP [1].

Continuum-Level Finite Element Modeling of the Optic Nerve Head Using a Fabric Tensor Based Description of the Lamina Cribrosa

2007 ◽  
Author(s):  
Michael D. Roberts ◽  
Richard T. Hart ◽  
Yi Liang ◽  
Anthony J. Bellezza ◽  
Claude F. Burgoyne ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Optic Nerve Head ◽  
Ganglion Cells ◽  
Lamina Cribrosa ◽  
Vision Impairment ◽  
Porous Space ◽  
Fabric Tensor ◽  
Retinal Ganglion ◽  
Pass Through ◽  
Connective Tissue Structure

Glaucoma is a chronic disease of the eye that can progress to severe vision impairment or blindness if left untreated. The principal site of glaucomatous damage is believed to be within the optic nerve head (ONH) where the axons of the retinal ganglion cells pass through an opening in the back of the sclera (the eye wall) on their way to form the orbital optic nerve. This opening is spanned by the lamina cribrosa (LC), a fenestrated connective tissue structure which provides both a load bearing function for the eye as well as support (both structural and metabolic) for axonal bundles as they traverse the porous space of the LC.

scholarly journals Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma

2007 ◽  
Vol 179 (7) ◽  
pp. 1523-1537 ◽  
Author(s):  
Gareth R. Howell ◽  
Richard T. Libby ◽  
Tatjana C. Jakobs ◽  
Richard S. Smith ◽  
F. Campbell Phalan ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Mouse Model ◽  
Retinal Ganglion Cells ◽  
Strong Evidence ◽  
Ganglion Cells ◽  
Lamina Cribrosa ◽  
Retinal Ganglion ◽  
Rich Region ◽  
Pattern Electroretinography ◽  
Axon Damage

Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network of astrocytes associates intimately with RGC axons. Using BAX-deficient DBA/2J mice, which retain all of their RGCs, we provide experimental evidence for an insult within or very close to the lamina in the optic nerve. We show that proximal axon segments attached to their cell bodies survive to the proximity of the lamina. In contrast, axon segments in the lamina and behind the eye degenerate. Finally, the Wlds allele, which is known to protect against insults to axons, strongly protects against DBA/2J glaucoma and preserves RGC activity as measured by pattern electroretinography. These experiments provide strong evidence for a local insult to axons in the optic nerve.

scholarly journals Retinal Ganglion Cells Downregulate Gene Expression and Lose Their Axons within the Optic Nerve Head in a Mouse Glaucoma Model

2008 ◽  
Vol 28 (2) ◽  
pp. 548-561 ◽  
Author(s):  
I. Soto ◽  
E. Oglesby ◽  
B. P. Buckingham ◽  
J. L. Son ◽  
E. D. O. Roberson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Optic Nerve Head ◽  
Ganglion Cells ◽  
Retinal Ganglion

Measuring the Biaxial Stress-Strain Characteristics of Human Sclera

2007 ◽  
Author(s):  
C. G. Olesen ◽  
I. Tertinegg ◽  
A. Eilaghi ◽  
G. W. Brodland ◽  
C. Horst ◽  
...  
Keyword(s):  
Risk Factor ◽  
Intraocular Pressure ◽  
Optic Nerve ◽  
Ganglion Cell ◽  
Mechanical Strain ◽  
Biaxial Stress ◽  
Retinal Ganglion ◽  
Irreversible Loss ◽  
Elevated Intraocular Pressure ◽  
Primary Risk Factor

Glaucoma is a common ocular disease that causes irreversible loss of vision. Elevated intraocular pressure (IOP) is the primary risk factor for developing glaucoma. It is believed that increased IOP causes mechanical strain on the glial cells that support the retinal ganglion cell axons and thereby causes ganglion cell apoptosis [1,2]. This damage occurs in the optic nerve head (ONH) region of the eye, and is important for understanding ONH biomechanics.

scholarly journals A Methodology for Individual-Specific Modeling of Rat Optic Nerve Head Biomechanics in Glaucoma

2018 ◽  
Vol 140 (8) ◽  
Author(s):  
Stephen A. Schwaner ◽  
Alison M. Kight ◽  
Robert N. Perry ◽  
Marta Pazos ◽  
Hongli Yang ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Optic Nerve Head ◽  
Cellular Response ◽  
Ganglion Cells ◽  
Axonal Injury ◽  
Retinal Ganglion ◽  
Mechanistic Studies ◽  
Specific Modeling ◽  
Initial Results ◽  
Model Strain

Glaucoma is the leading cause of irreversible blindness and involves the death of retinal ganglion cells (RGCs). Although biomechanics likely contributes to axonal injury within the optic nerve head (ONH), leading to RGC death, the pathways by which this occurs are not well understood. While rat models of glaucoma are well-suited for mechanistic studies, the anatomy of the rat ONH is different from the human, and the resulting differences in biomechanics have not been characterized. The aim of this study is to describe a methodology for building individual-specific finite element (FE) models of rat ONHs. This method was used to build three rat ONH FE models and compute the biomechanical environment within these ONHs. Initial results show that rat ONH strains are larger and more asymmetric than those seen in human ONH modeling studies. This method provides a framework for building additional models of normotensive and glaucomatous rat ONHs. Comparing model strain patterns with patterns of cellular response seen in studies using rat glaucoma models will help us to learn more about the link between biomechanics and glaucomatous cell death, which in turn may drive the development of novel therapies for glaucoma.

scholarly journals An Overview of Glaucoma: Bidirectional Translation between Humans and Pre-Clinical Animal Models

2021 ◽  
Author(s):  
Sophie Pilkinton ◽  
T.J. Hollingsworth ◽  
Brian Jerkins ◽  
Monica M. Jablonski
Keyword(s):  
Risk Factor ◽  
Intraocular Pressure ◽  
Optic Nerve ◽  
Animal Models ◽  
Retinal Ganglion Cells ◽  
Optic Nerve Head ◽  
Ganglion Cells ◽  
Treatment Modalities ◽  
Retinal Ganglion ◽  
Glaucomatous Damage

Glaucoma is a multifactorial, polygenetic disease with a shared outcome of loss of retinal ganglion cells and their axons, which ultimately results in blindness. The most common risk factor of this disease is elevated intraocular pressure (IOP), although many glaucoma patients have IOPs within the normal physiological range. Throughout disease progression, glial cells in the optic nerve head respond to glaucomatous changes, resulting in glial scar formation as a reaction to injury. This chapter overviews glaucoma as it affects humans and the quest to generate animal models of glaucoma so that we can better understand the pathophysiology of this disease and develop targeted therapies to slow or reverse glaucomatous damage. This chapter then reviews treatment modalities of glaucoma. Revealed herein is the lack of non-IOP-related modalities in the treatment of glaucoma. This finding supports the use of animal models in understanding the development of glaucoma pathophysiology and treatments.

scholarly journals Image-Based Modeling of Optic Nerve Head Mechanics Following Lumbar Puncture

2017 ◽  
Author(s):  
Junfei Tong ◽  
Deepta Ghate ◽  
Sachin Kedar ◽  
Linxia Gu
Keyword(s):  
Optic Nerve ◽  
Lumbar Puncture ◽  
Optic Nerve Head ◽  
Computational Models ◽  
Cell Damage ◽  
Open Angle Glaucoma ◽  
Element Model ◽  
Lamina Cribrosa ◽  
Image Based Modeling

Biomechanics of optic nerve head (ONH) has attracted increasing attention in recent years due to its association with ganglion cell damage and tissue remodeling resulted vision impairments [1, 2]. The ONH is exposed to both intraocular pressure (IOP) and intracranial pressure (ICP), separated by the lamina cribrosa (LC) which is regarded as the primary site of axonal injury in glaucoma[3]. The elevated IOP was widely acknowledged as a major risk factor for glaucoma. However, a large number of glaucoma patients never have an increase in IOP [4]. In studies that have looked at lumbar puncture (LP) data, patients with open-angle glaucoma were found to have lower ICPs than non-glaucomatous controls[5]. It suggests that higher translaminar pressure difference across the LC rather than IOP alone may have an important role in the pathogenesis of ONH damage. There were few computational models had been established to investigate the ICP’s role on ONH, such as Ethier et al. found elevated ICP could induce decreased strain within LC using finite element model[6]. However, less experimental data are available for delineating the role of ICP on the behaviors of LC. In this work, we present one dataset from LP patients and reconstruct its two-dimensional computational model of the ONH based on the patient’s images to delineate the role of ICP on ONH mechanics. The changes of LC depth, BMO width and papillary height were compared between the simulation and clinical dataset. The maximum principal strain of LC was calculated to reinforce its link with mechanosensitive cells in ONH.

scholarly journals Factors affecting optic nerve head biomechanics in a rat model of glaucoma

2020 ◽  
Vol 17 (165) ◽  
pp. 20190695 ◽  
Author(s):  
Stephen A. Schwaner ◽  
Andrew J. Feola ◽  
C. Ross Ethier
Keyword(s):  
Optic Nerve ◽  
Optic Nerve Head ◽  
Ganglion Cells ◽  
Disease Process ◽  
Collagen Fibre ◽  
Sensitivity Study ◽  
Ground Substance ◽  
Retinal Ganglion ◽  
Factors Affecting ◽  
Ganglion Cell Death

Glaucoma is the leading cause of irreversible blindness and is characterized by the death of retinal ganglion cells, which carry vision information from the retina to the brain. Although it is well accepted that biomechanics is an important part of the glaucomatous disease process, the mechanisms by which biomechanical insult, usually due to elevated intraocular pressure (IOP), leads to retinal ganglion cell death are not understood. Rat models of glaucoma afford an opportunity for learning more about these mechanisms, but the biomechanics of the rat optic nerve head (ONH), a primary region of damage in glaucoma, are only just beginning to be characterized. In a previous study, we built finite-element models with individual-specific rat ONH geometries. Here, we developed a parametrized model of the rat ONH and used it to perform a sensitivity study to determine the influence that six geometric parameters and 13 tissue material properties have on rat optic nerve biomechanical strains due to IOP elevation. Strain magnitudes and patterns in the parametrized model generally matched those from individual-specific models, suggesting that the parametrized model sufficiently approximated rat ONH anatomy. Similar to previous studies in human eyes, we found that scleral properties were highly influential: the six parameters with highest influence on optic nerve strains were optic nerve stiffness, IOP, scleral thickness, the degree of alignment of scleral collagen fibres, scleral ground substance stiffness and the scleral collagen fibre uncrimping coefficient. We conclude that a parametrized modelling strategy is an efficient approach that allows insight into rat ONH biomechanics. Further, scleral properties are important influences on rat ONH biomechanics, and additional efforts should be made to better characterize rat scleral collagen fibre organization.

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

2020 ◽  
Vol 143 (4) ◽  
Author(s):  
Stephen A. Schwaner ◽  
Robert N. Perry ◽  
Alison M. Kight ◽  
Emily Winder ◽  
Hongli Yang ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Optic Nerve Head ◽  
Ganglion Cells ◽  
Fiber Direction ◽  
Retinal Ganglion ◽  
Main Site ◽  
Specific Geometry ◽  
Specific Modeling ◽  
The Brain ◽  
Do So

Abstract Glaucoma is the second leading cause of blindness worldwide and is characterized by the death of retinal ganglion cells (RGCs), the cells that send vision information to the brain. Their axons exit the eye at the optic nerve head (ONH), the main site of damage in glaucoma. The importance of biomechanics in glaucoma is indicated by the fact that elevated intraocular pressure (IOP) is a causative risk factor for the disease. However, exactly how biomechanical insult leads to RGC death is not understood. Although rat models are widely used to study glaucoma, their ONH biomechanics have not been characterized in depth. Therefore, we aimed to do so through finite element (FE) modeling. Utilizing our previously described method, we constructed and analyzed ONH models with individual-specific geometry in which the sclera was modeled as a matrix reinforced with collagen fibers. We developed eight sets of scleral material parameters based on results from our previous inverse FE study and used them to simulate the effects of elevated IOP in eight model variants of each of seven rat ONHs. Within the optic nerve, highest strains were seen inferiorly, a pattern that was consistent across model geometries and model variants. In addition, 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 be used to interpret data from rat glaucoma studies to learn more about how biomechanics affects RGC pathogenesis in glaucoma.

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