Optic nerve head biomechanics in aging and disease

Downs, J. Crawford

doi:10.1016/j.exer.2015.02.011

Cited by 139Glaucoma and retinal disordersCorneal surgery and disordersElasticity and Material Modeling

Optic nerve head biomechanics in aging and disease

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Downs, J. Crawford·2015·Experimental Eye Research

DOI 10.1016/j.exer.2015.02.011PMC PMC4379445

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Abstract

This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression.

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Old mice develop opaque lenses and lose retinal ganglion cells in the innermost retinal layer.
“Old mice develop opaque lenses and lose retinal ganglion cells (RGCs) in the innermost retinal layer (Calkins, 2013; Downs, 2015; Samuel et al., 2011; Wolf et al., 2000) (Figure 7J).”
From Loss of epigenetic information as a cause of mammalian aging (2023) · cites this paper as Downs, 2015
Section 3.A (Aging; page unavailable) discusses retinal ganglion cell loss in an experimental mouse model of glaucoma. It does not say that aging itself causes this loss in mice, and the passages found on lens opacity do not support the claim about opaque lenses. (LLM, conf=0.82)
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Theory of elasticity
Timoshenko, S. P., & Goodier, J. N. (1934) · Virtual Defense Library (Ministerio de Defensa) · Cited by 13,717 · see citing works
The number of people with glaucoma worldwide in 2010 and 2020
Quigley, H. A. (2006) · British Journal of Ophthalmology · doi:10.1136/bjo.2005.081224 · Cited by 7,417 · see citing works
The Ocular Hypertension Treatment Study
Gordon, M. O. (2002) · Archives of Ophthalmology · doi:10.1001/archopht.120.6.714 · Cited by 2,638 · see citing works
Factors for Glaucoma Progression and the Effect of Treatment
Leske, M. C. (2003) · Archives of Ophthalmology · doi:10.1001/archopht.121.1.48 · Cited by 2,036 · see citing works
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
Burgoyne, C. F., Downs, J. C., Bellezza, A. J., Suh, J.-K. F., & Hart, R. T. (2004) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2004.06.001 · Cited by 1,142 · see citing works
Self-citation
Mechanisms of maturation and ageing of collagen
Bailey, A. J., Paul, R. G., & Knott, L. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00119-5 · Cited by 672 · see citing works
Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma
Howell, G. R., Libby, R. T., Jakobs, T., Smith, R. S., Phalan, F. C., Barter, J. W., Barbay, J. M., Marchant, J. K., Nagaraju, M., Porciatti, V., et al. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200706181 · Cited by 593 · see citing works
The optic nerve head in glaucoma: role of astrocytes in tissue remodeling
Hernandez, M. R. (2000) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(99)00017-8 · Cited by 565 · see citing works
Factors Influencing Optic Nerve Head Biomechanics
Sigal, I. A., Flanagan, J. G., & Ethier, C. R. (2005) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.05-0541 · Cited by 509 · see citing works
Variations in Primary Open-Angle Glaucoma Prevalence by Age, Gender, and Race: A Bayesian Meta-Analysis
Rudnicka, A. R., Mt‐Isa, S., Owen, C. G., Cook, D. G., & Ashby, D. (2006) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0299 · Cited by 501 · see citing works
Cerebrospinal Fluid Pressure Is Decreased in Primary Open-angle Glaucoma
Berdahl, J. P., Allingham, R. R., & Johnson, D. H. (2008) · Ophthalmology · doi:10.1016/j.ophtha.2008.01.013 · Cited by 428 · see citing works
A biomechanical paradigm for axonal insult within the optic nerve head in aging and glaucoma
Burgoyne, C. F. (2010) · Experimental Eye Research · doi:10.1016/j.exer.2010.09.005 · Cited by 393 · see citing works
The eye and the heart
Flammer, J., Konieczka, K., Bruno, R. M., Virdis, A., Flammer, A. J., & Taddei, S. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht023 · Cited by 389 · see citing works
Chronic experimental glaucoma in primates. II. Effect of extended intraocular pressure elevation on optic nerve head and axonal transport.
Quigley, H. A., & Addicks, E. M. (1980) · PubMed · Cited by 354 · see citing works
Human sclera: Thickness and surface area
Olsen, T. W., Aaberg, S., Geroski, D. H., & Edelhauser, H. F. (1998) · American Journal of Ophthalmology · doi:10.1016/s0002-9394(99)80096-8 · Cited by 349 · see citing works
Under Pressure: Cellular and Molecular Responses During Glaucoma, a Common Neurodegeneration with Axonopathy
Nickells, R. W., Howell, G. R., Soto, I., & John, S. W. M. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135728 · Cited by 338 · see citing works
Biomechanics of the Human Posterior Sclera: Age- and Glaucoma-Related Changes Measured Using Inflation Testing
Coudrillier, B., Tian, J., Alexander, S., et al. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-8009 · Cited by 335 · see citing works
The dynamics and location of axonal transport blockade by acute intraocular pressure elevation in primate optic nerve.
Quigley, H. A., & Anderson, D. R. (1976) · PubMed · Cited by 317 · see citing works
Mechanical Environment of the Optic Nerve Head in Glaucoma
Downs, J. C., Roberts, M. D., & Burgoyne, C. F. (2008) · Optometry and Vision Science · doi:10.1097/opx.0b013e31817841cb · Cited by 252 · see citing works
Self-citation
Age related compliance of the lamina cribrosa in human eyes
Albon, J. (2000) · British Journal of Ophthalmology · doi:10.1136/bjo.84.3.318 · Cited by 247 · see citing works
3-D Histomorphometry of the Normal and Early Glaucomatous Monkey Optic Nerve Head: Lamina Cribrosa and Peripapillary Scleral Position and Thickness
Yang, H., Downs, J. C., Girkin, C. A., et al. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0349 · Cited by 245 · see citing works
Self-citation
Glaucomatous cupping of the lamina cribrosa: A review of the evidence for active progressive remodeling as a mechanism
Downs, J. C., Roberts, M. D., & Sigal, I. A. (2010) · Experimental Eye Research · doi:10.1016/j.exer.2010.08.004 · Cited by 229 · see citing works
Self-citation
Dimensions of the human sclera: Thickness measurement and regional changes with axial length
Norman, R., Flanagan, J. G., Rausch, S., et al. (2009) · Experimental Eye Research · doi:10.1016/j.exer.2009.11.001 · Cited by 228 · see citing works
Effects of raised intraocular pressure on retinal, prelaminar, laminar, and retrolaminar optic nerve blood flow in monkeys.
Geijer, C., & Bill, A. (1979) · PubMed · Cited by 223 · see citing works
Biomechanical Changes in the Sclera of Monkey Eyes Exposed to Chronic IOP Elevations
Girard, M. J. A., Suh, J.-K. F., Bottlang, M., et al. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6927 · Cited by 221 · see citing works
Therapeutic potential of breakers of advanced glycation end product–protein crosslinks
Vasan, S., Foiles, P. G., & Founds, H. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.08.016 · Cited by 221 · see citing works
Premise and Prediction???How Optic Nerve Head Biomechanics Underlies the Susceptibility and Clinical Behavior of the Aged Optic Nerve Head
Burgoyne, C. F., & Downs, J. C. (2008) · Journal of Glaucoma · doi:10.1097/ijg.0b013e31815a343b · Cited by 213 · see citing works
Self-citation
Scleral Biomechanics in the Aging Monkey Eye
Girard, M. J. A., Suh, J.-K. F., Bottlang, M., et al. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-3363 · Cited by 213 · see citing works
Remodeling of the Connective Tissue Microarchitecture of the Lamina Cribrosa in Early Experimental Glaucoma
Roberts, M. D., Grau, V., Grimm, J. L., Reynaud, J. F., Bellezza, A. J., Burgoyne, C. F., & Downs, J. C. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-1792 · Cited by 207 · see citing works
Self-citation
Optic Nerve Head Extracellular Matrix in Primary Optic Atrophy and Experimental Glaucoma
Morrison, J. C. (1990) · Archives of Ophthalmology · doi:10.1001/archopht.1990.01070090122053 · Cited by 201 · see citing works
Finite element modeling of the human sclera: Influence on optic nerve head biomechanics and connections with glaucoma
Norman, R., Flanagan, J. G., Sigal, I. A., et al. (2010) · Experimental Eye Research · doi:10.1016/j.exer.2010.09.014 · Cited by 199 · see citing works
Laminar and Prelaminar Tissue Displacement During Intraocular Pressure Elevation in Glaucoma Patients and Healthy Controls
Agoumi, Y., Sharpe, G. P., Hutchison, D. M., et al. (2010) · Ophthalmology · doi:10.1016/j.ophtha.2010.05.016 · Cited by 198 · see citing works
Mechanical Strain Stabilizes Reconstituted Collagen Fibrils against Enzymatic Degradation by Mammalian Collagenase Matrix Metalloproteinase 8 (MMP-8)
Flynn, B. P., Bhole, A. P., Saeidi, N., Liles, M., DiMarzio, C. A., & Ruberti, J. W. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012337 · Cited by 196 · see citing works
Age-Related Differences in the Elasticity of the Human Cornea
Cartwright, N. E. K., Tyrer, J. R., & Marshall, J. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-4798 · Cited by 194 · see citing works
Three-Dimensional Reconstruction of Normal and Early Glaucoma Monkey Optic Nerve Head Connective Tissues
Burgoyne, C. F., Downs, J. C., Bellezza, A. J., et al. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-0022 · Cited by 191 · see citing works
Self-citation
Optic disc movement with variations in intraocular and cerebrospinal fluid pressure.
Morgan, W. H., Chauhan, B. C., Yu, D., et al. (2002) · PubMed · Cited by 187 · see citing works
Cerebrospinal Fluid Pressure Decreases with Older Age
Fleischman, D., Berdahl, J. P., Zaydlarova, J., Stinnett, S. S., Fautsch, M. P., & Allingham, R. R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052664 · Cited by 183 · see citing works
Predicted extension, compression and shearing of optic nerve head tissues
Sigal, I. A., Flanagan, J. G., Tertinegg, I., et al. (2007) · Experimental Eye Research · doi:10.1016/j.exer.2007.05.005 · Cited by 181 · see citing works
The morphology and spatial arrangement of astrocytes in the optic nerve head of the mouse
Sun, D., Lye‐Barthel, M., Masland, R. H., & Jakobs, T. (2009) · The Journal of Comparative Neurology · doi:10.1002/cne.22058 · Cited by 180 · see citing works
Distribution of axonal transport blockade by acute intraocular pressure elevation in the primate optic nerve head.
Quigley, H. A., & Anderson, D. R. (1977) · PubMed · Cited by 171 · see citing works
Advanced Maillard Reaction and Crosslinking of Corneal Collagen in Diabetes
Sady, C., Khosrof, S., & Nagaraj, R. H. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2356 · Cited by 171 · see citing works
Posterior (Outward) Migration of the Lamina Cribrosa and Early Cupping in Monkey Experimental Glaucoma
Yang, H., Williams, G. A., Downs, J. C., Sigal, I. A., Roberts, M. D., Thompson, H. W., & Burgoyne, C. F. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-7448 · Cited by 170 · see citing works
Self-citation
Three-Dimensional Histomorphometry of the Normal and Early Glaucomatous Monkey Optic Nerve Head: Neural Canal and Subarachnoid Space Architecture
Downs, J. C., Yang, H., Girkin, C. A., et al. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0021 · Cited by 169 · see citing works
Self-citation
Quantitative Mapping of Collagen Fiber Orientation in Non-glaucoma and Glaucoma Posterior Human Sclerae
Pijanka, J. K., Coudrillier, B., Ziegler, K. A., et al. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-9705 · Cited by 167 · see citing works
Changes in the collagenous matrix of the aging human lamina cribrosa.
Albon, J., KARWATOWSKI, W. S. S., Avery, N., et al. (1995) · British Journal of Ophthalmology · doi:10.1136/bjo.79.4.368 · Cited by 166 · see citing works
Vascular aging: From molecular mechanism to clinical significance
Sawabe, M. (2010) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2010.00603.x · Cited by 164 · see citing works
Anterior and Posterior Optic Nerve Head Blood Flow in Nonhuman Primate Experimental Glaucoma Model Measured by Laser Speckle Imaging Technique and Microsphere Method
Wang, L., Cull, G. A., Piper, C., et al. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-10911 · Cited by 164 · see citing works
IOP-Induced Lamina Cribrosa Displacement and Scleral Canal Expansion: An Analysis of Factor Interactions Using Parameterized Eye-Specific Models
Sigal, I. A., Yang, H., Roberts, M. D., et al. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-5500 · Cited by 162 · see citing works
Influence of cyclical mechanical strain on extracellular matrix gene expression in human lamina cribrosa cells in vitro.
Kirwan, R. P., Fenerty, C., Crean, J. K. G., Wordinger, R. J., Clark, A. F., & O'Brien, C. J. (2005) · PubMed · Cited by 147 · see citing works
Age-Related Changes in the Extracellular Matrix of the Human Optic Nerve Head
Hernandez, M. R., Luo, X. X., Andrzejewska, W. M., et al. (1989) · American Journal of Ophthalmology · doi:10.1016/0002-9394(89)90491-1 · Cited by 145 · see citing works
24-Hour IOP Telemetry in the Nonhuman Primate: Implant System Performance and Initial Characterization of IOP at Multiple Timescales
Downs, J. C., Burgoyne, C. F., Seigfreid, W. P., et al. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-7955 · Cited by 143 · see citing works
Self-citation
Age-related variations in the biomechanical properties of human sclera
Geraghty, B., Jones, S., Rama, P., Akhtar, R., & Elsheikh, A. (2012) · Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · doi:10.1016/j.jmbbm.2012.10.011 · Cited by 138 · see citing works
Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP
Resta, V., Novelli, E., Vozzi, G., Scarpa, C., Caleo, M., Ahluwalia, A. D., Solini, A., Santini, E., Parisi, V., Virgilio, F. D., et al. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05528.x · Cited by 137 · see citing works
Correlation between Local Stress and Strain and Lamina Cribrosa Connective Tissue Volume Fraction in Normal Monkey Eyes
Roberts, M. D., Liang, Y., Sigal, I. A., et al. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-4016 · Cited by 136 · see citing works
Age- and Race-Related Differences in Human Scleral Material Properties
Grytz, R., Fazio, M. A., Libertiaux, V., et al. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-14029 · Cited by 136 · see citing works
The Relation Between Glaucomatous Damage and Optic Nerve Head Mechanical Compliance
Zeimer, R. C. (1989) · Archives of Ophthalmology · doi:10.1001/archopht.1989.01070020298042 · Cited by 132 · see citing works
Scleral anisotropy and its effects on the mechanical response of the optic nerve head
Coudrillier, B., Boote, C., Quigley, H. A., et al. (2012) · Biomechanics and Modeling in Mechanobiology · doi:10.1007/s10237-012-0455-y · Cited by 132 · see citing works
Effect of Acute Intraocular Pressure Elevation on the Monkey Optic Nerve Head as Detected by Spectral Domain Optical Coherence Tomography
Strouthidis, N. G., Fortune, B. A., Yang, H., et al. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-7922 · Cited by 131 · see citing works
Eye-Specific IOP-Induced Displacements and Deformations of Human Lamina Cribrosa
Sigal, I. A., Grimm, J. L., Jan, N., et al. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-12724 · Cited by 130 · see citing works
Optic Neuropathy Induced by Experimentally Reduced Cerebrospinal Fluid Pressure in Monkeys
Yang, D., Fu, J., Hou, R., et al. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-13657 · Cited by 130 · see citing works
Viscoelastic Characterization of Peripapillary Sclera: Material Properties by Quadrant in Rabbit and Monkey Eyes
Downs, J. C., Suh, J.-K. F., Thomas, K. A., et al. (2003) · Journal of Biomechanical Engineering · doi:10.1115/1.1536930 · Cited by 129 · see citing works
Self-citation
Material properties of the posterior human sclera
Grytz, R., Fazio, M. A., Girard, M. J. A., et al. (2013) · Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · doi:10.1016/j.jmbbm.2013.03.027 · Cited by 129 · see citing works
Intracranial pressure and glaucoma
Berdahl, J. P., & Allingham, R. R. (2010) · Current Opinion in Ophthalmology · doi:10.1097/icu.0b013e32833651d8 · Cited by 124 · see citing works
Expression of bone morphogenetic proteins (BMP), BMP receptors, and BMP associated proteins in human trabecular meshwork and optic nerve head cells and tissues.
Wordinger, R. J., Agarwal, R., Talati, M., Fuller, J., Lambert, W. S., & Clark, A. F. (2002) · PubMed · Cited by 124 · see citing works
IOP-Induced Lamina Cribrosa Deformation and Scleral Canal Expansion: Independent or Related?
Sigal, I. A., Yang, H., Roberts, M. D., et al. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-8183 · Cited by 123 · see citing works
Deformation of the Normal Monkey Optic Nerve Head Connective Tissue after Acute IOP Elevation within 3-D Histomorphometric Reconstructions
Yang, H., Downs, J. C., Sigal, I. A., Roberts, M. D., Thompson, H. W., & Burgoyne, C. F. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-3410 · Cited by 122 · see citing works
Self-citation
Age‐related changes to the molecular and cellular components of equine flexor tendons
Birch, H. L., Bailey, J. V., Bailey, A. J., et al. (1999) · Equine Veterinary Journal · doi:10.1111/j.2042-3306.1999.tb03838.x · Cited by 121 · see citing works
Differential expression of matrix metalloproteinases in monkey eyes with experimental glaucoma or optic nerve transection
Agapova, O. A., Kaufman, P. L., Lucarelli, M. J., et al. (2003) · Brain Research · doi:10.1016/s0006-8993(02)04234-8 · Cited by 111 · see citing works
Intrinsic axonal degeneration pathways are critical for glaucomatous damage
Howell, G. R., Soto, I., Libby, R. T., & John, S. W. M. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.01.014 · Cited by 110 · see citing works
Studies of Scleral Biomechanical Behavior Related to Susceptibility for Retinal Ganglion Cell Loss in Experimental Mouse Glaucoma
Nguyen, C., Cone, F. E., Nguyen, T. D., Coudrillier, B., Pease, M. E., Steinhart, M. R., Oglesby, E., Jefferys, J. L., & Quigley, H. A. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-10952 · Cited by 105 · see citing works
Lamina cribrosa thickening in early glaucoma predicted by a microstructure motivated growth and remodeling approach
Grytz, R., Sigal, I. A., Ruberti, J. W., et al. (2011) · Mechanics of Materials · doi:10.1016/j.mechmat.2011.07.004 · Cited by 101 · see citing works
Changes in the Biomechanical Response of the Optic Nerve Head in Early Experimental Glaucoma
Roberts, M. D., Sigal, I. A., Liang, Y., Burgoyne, C. F., & Downs, J. C. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-5411 · Cited by 100 · see citing works
Self-citation
Biomechanics of the Posterior Eye: A Critical Role in Health and Disease
Campbell, I. C., Coudrillier, B., & Ethier, C. R. (2013) · Journal of Biomechanical Engineering · doi:10.1115/1.4026286 · Cited by 99 · see citing works
Age-related changes in human peripapillary scleral strain
Fazio, M. A., Grytz, R., Morris, J. S., et al. (2013) · Biomechanics and Modeling in Mechanobiology · doi:10.1007/s10237-013-0517-9 · Cited by 98 · see citing works
The role of matricellular proteins in glaucoma
Wallace, D., Murphy-Ullrich, J. E., Downs, J. C., & O'Brien, C. J. (2014) · Matrix Biology · doi:10.1016/j.matbio.2014.03.007 · Cited by 97 · see citing works
Self-citation
Rates of Neuroretinal Rim and Peripapillary Atrophy Area Change
See, J. L. S., Nicolela, M. T., & Chauhan, B. C. (2009) · Ophthalmology · doi:10.1016/j.ophtha.2008.12.005 · Cited by 95 · see citing works
Neuronal Response to High Rate Shear Deformation Depends on Heterogeneity of the Local Strain Field
Cullen, D., & LaPlaca, M. (2006) · Journal of Neurotrauma · doi:10.1089/neu.2006.23.1304 · Cited by 94 · see citing works
Transforming growth factor-β2 increases extracellular matrix proteins in optic nerve head cells via activation of the Smad signaling pathway.
Zode, G. S., Sethi, A., Brun‐Zinkernagel, A., et al. (2011) · PubMed · Cited by 91 · see citing works
Influence of cyclical mechanical strain on extracellular matrix gene expression in human lamina cribrosa cells in vitro
O'Brien, C. J., Kirwan, R. P., Fenerty, C., et al. (2006) · Journal of Biomechanics · doi:10.1016/s0021-9290(06)84552-5 · Cited by 89 · see citing works
Structural Proteins of the Neonatal and Adult Lamina Cribrosa
Morrison, J. C. (1989) · Archives of Ophthalmology · doi:10.1001/archopht.1989.01070020286040 · Cited by 87 · see citing works
Impact of aging and diet restriction on retinal function during and after acute intraocular pressure injury
Kong, Y. X. G., Bergen, N. V., Bui, B. V., Chrysostomou, V., Vingrys, A. J., Trounce, I. A., & Crowston, J. G. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.11.026 · Cited by 85 · see citing works
Glaucoma: Changes in Extracellular Matrix in the Optic Nerve Head
Hernandez, M. R., & Ye, H. (1993) · Annals of Medicine · doi:10.3109/07853899309147290 · Cited by 82 · see citing works
Human Scleral Structural Stiffness Increases More Rapidly With Age in Donors of African Descent Compared to Donors of European Descent
Fazio, M. A., Grytz, R., Morris, J. S., et al. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-14894 · Cited by 78 · see citing works
Regional Variations in Mechanical Strain in the Posterior Human Sclera
Fazio, M. A., Grytz, R., Bruno, L., et al. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-9668 · Cited by 76 · see citing works
Corneal Stiffness Affects IOP Elevation during Rapid Volume Change in the Eye
Liu, J., & He, X. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-2365 · Cited by 75 · see citing works
Bone morphogenetic protein 4 inhibits TGF‐β2 stimulation of extracellular matrix proteins in optic nerve head cells: Role of gremlin in ECM modulation
Zode, G. S., Clark, A. F., & Wordinger, R. J. (2008) · Glia · doi:10.1002/glia.20803 · Cited by 75 · see citing works
Perspectives on biomechanical growth and remodeling mechanisms in glaucoma
Grytz, R., Girkin, C. A., Libertiaux, V., & Downs, J. C. (2012) · Mechanics Research Communications · doi:10.1016/j.mechrescom.2012.01.007 · Cited by 73 · see citing works
Self-citation
Microstructural Differences in the Human Posterior Sclera as a Function of Age and Race
Yan, D., McPheeters, S., Johnson, G., et al. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-4651 · Cited by 71 · see citing works
Integrins in the optic nerve head: potential roles in glaucomatous optic neuropathy (an American Ophthalmological Society thesis).
Morrison, J. C. (2006) · PubMed · Cited by 70 · see citing works
In Vivo Three-Dimensional Characterization of the Healthy Human Lamina Cribrosa With Adaptive Optics Spectral-Domain Optical Coherence Tomography
Nadler, Z., Wang, B., Schuman, J. S., et al. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-15177 · Cited by 63 · see citing works
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Wallace, D., Clark, A. F., Lipson, K. E., et al. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-12494 · Cited by 59 · see citing works
Peripapillary scleral thickness in perfusion-fixed normal monkey eyes.
Downs, J. C., Blidner, R., Bellezza, A. J., et al. (2002) · PubMed · Cited by 54 · see citing works
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Cull, G. A., Burgoyne, C. F., Fortune, B. A., & Wang, L. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-12013 · Cited by 49 · see citing works
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Morris, H. J., Tang, J., Perez, B. C., et al. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-12441 · Cited by 48 · see citing works
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Wang, L., Cull, G. A., Burgoyne, C. F., Thompson, S. J., & Fortune, B. A. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-14020 · Cited by 43 · see citing works
Elevated pressure induced astrocyte damage in the optic nerve
Balaratnasingam, C., Morgan, W. H., Bass, L., et al. (2008) · Brain Research · doi:10.1016/j.brainres.2008.09.044 · Cited by 42 · see citing works
3D modeling to characterize lamina cribrosa surface and pore geometries using in vivo images from normal and glaucomatous eyes
Sredar, N., Ivers, K. M., Queener, H. M., et al. (2013) · Biomedical Optics Express · doi:10.1364/boe.4.001153 · Cited by 41 · see citing works
Multiscale finite element modeling of the lamina cribrosa microarchitecture in the eye
Downs, J. C., Roberts, M. D., Burgoyne, C. F., et al. (2009) · doi:10.1109/iembs.2009.5332755 · Cited by 40 · see citing works
Self-citation
Susceptibility to glaucoma damage related to age and connective tissue mutations in mice
Steinhart, M. R., Cone-Kimball, E., Nguyen, C., et al. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.12.008 · Cited by 36 · see citing works
Factors Affecting Plastic Lamina Cribrosa Displacement in Glaucoma Patients
Jung, K. I., Jung, Y., Park, K. T., et al. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-13957 · Cited by 29 · see citing works
European Society of Biomechanics S.M. Perren Award 2010: An adaptation mechanism for fibrous tissue to sustained shortening
Foolen, J., van Donkelaar, C. C., Soekhradj-Soechit, S., et al. (2010) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2010.07.040 · Cited by 25 · see citing works
Optic Nerve Fast Axonal Transport Abnormalities in Primates
Radius, R. L. (1980) · Archives of Ophthalmology · doi:10.1001/archopht.1980.01020040870017 · Cited by 24 · see citing works
Scleral Permeability Varies by Mouse Strain and Is Decreased by Chronic Experimental Glaucoma
Pease, M. E., Oglesby, E., Cone-Kimball, E., et al. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-13327 · Cited by 20 · see citing works
Cerebrospinal fluid pressure and glaucomatous optic disc cupping
Berdahl, J. P., Ethier, C. R., & Allingham, R. R. (2009) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-009-1110-x · Cited by 14 · see citing works

Flagged first, then by citations

Research works printed but not linked: 2

Cioffi GA Van Buskirk EM 1996 Vasculature of the anterior optic nerve and peripapillary choroid The Glaucomas Ritch R Shields MB Krupin Mosby T Louis St Basic Sciences 177 197
Sigal IA Roberts MD Girard MJA Burgoyne CF Downs JC 2010 Chapter 20: Biomechanical Changes of the Optic Disc Ocular Disease: Mechanisms and Management Levin LA Albert DM London Elsevier 153 164

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Geest, J. P. V., & Yan, D. (2010) · Investigative Ophthalmology & Visual Science
Scleral Biomechanics in the Glaucomatous Monkey Eye
Girard, M. J. A., Suh, J. F., Bottlang, M., et al. (2009) · ASME Summer Bioengineering Conference (SBC) · doi:10.1115/sbc2009-206799 · Cited by 2 · see citing works
Effects of ocular dimensions on IOP-related stress within the optic nerve head and posterior scleral shell
Bellezza, A. J., Hart, R. T., Villarraga, M. L., et al. (2003) · doi:10.1109/iembs.1999.804480
Age-Related Changes in Scleral Material Properties of the Monkey Eye
Girard, M. J. A., Suh, J. F., Bottlang, M., et al. (2008) · ASME Summer Bioengineering Conference (SBC) · doi:10.1115/sbc2008-192833

Authors: Downs, J. C.
Affiliations: University of Alabama at Birmingham (US)
Corresponding author: Downs, J. Crawford
ORCID: Downs, J. Crawford
Venue: Experimental Eye Research
Publisher: Elsevier BV
Published: 2015-04
Volume: 133
Pages: 19-29
ISSN: 0014-4835 (ISSN-L)
DOI: 10.1016/j.exer.2015.02.011
PMC: PMC4379445
OpenAlex: W2121962174
Cited by: 139
References: 106
Citations by year: 2026: 4 · 2025: 7 · 2024: 12 · 2023: 8 · 2022: 19 · 2021: 16 · 2020: 16 · 2019: 17 · 2018: 11 · 2017: 13 · 2016: 13 · 2015: 3
FWCI: 2.47
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Eye Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: NIH (R01 EY-018926)
Topics: Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal surgery and disorders
Physical Sciences › Engineering › Biomedical Engineering › Elasticity and Material Modeling
Keywords: optic nerve head biomechanics, aging, glaucoma, intraocular pressure, lamina cribrosa, peripapillary sclera, extracellular matrix, mechanobiology, connective tissue response, blood flow, optic nerve head
MeSH terms: Aging, Biomechanical Phenomena, Computer Simulation, Humans, Models, Biological, Optic Disk, Optic Nerve Diseases, Finite Element Analysis

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Optic nerve head biomechanics in aging and disease

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