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2. Biomechanical aspects of axonal damage in glaucoma: A brief review

Author

Cheri Stowell, Claude F. Burgoyne, Ernst R. Tamm, C. Ross Ethier, John E. Dowling, Crawford Downs, Mark H. Ellisman, Steven Fisher, Brad Fortune, Marcus Fruttiger, Tatjana Jakobs, Geoffrey Lewis, Richard H. Masland, Claire H. Mitchell, John Morrison, Sansar C. Sharma, Ian Sigal, Michael Sofroniew, Lin Wang, Janey Wiggs, and Samuel Wu

Subjects
0301 basic medicine, Intraocular pressure, genetic structures, Open angle glaucoma, business.industry, Optic disk, Connective tissue, Glaucoma, medicine.disease, Retinal ganglion, eye diseases, Sensory Systems, 03 medical and health sciences, Cellular and Molecular Neuroscience, Ophthalmology, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, 030221 ophthalmology & optometry, Optic nerve, Medicine, sense organs, Cerebrospinal fluid pressure, business, Neuroscience
Abstract

The biomechanical environment within the optic nerve head (ONH) is complex and is likely directly involved in the loss of retinal ganglion cells (RGCs) in glaucoma. Unfortunately, our understanding of this process is poor. Here we describe factors that influence ONH biomechanics, including ONH connective tissue microarchitecture and anatomy; intraocular pressure (IOP); and cerebrospinal fluid pressure (CSFp). We note that connective tissue factors can vary significantly from one individual to the next, as well as regionally within an eye, and that the understanding of ONH biomechanics is hindered by anatomical differences between small-animal models of glaucoma (rats and mice) and humans. Other challenges of using animal models of glaucoma to study the role of biomechanics include the complexity of assessing the degree of glaucomatous progression; and inadequate tools for monitoring and consistently elevating IOP in animal models. We conclude with a consideration of important open research questions/challenges in this area, including: (i) Creating a systems biology description of the ONH; (ii) addressing the role of astrocyte connective tissue remodeling and reactivity in glaucoma; (iii) providing a better characterization of ONH astrocytes and non-astrocytic constituent cells; (iv) better understanding the role of ONH astrocyte phagocytosis, proliferation and death; (v) collecting gene expression and phenotype data on a larger, more coordinated scale; and (vi) developing an implantable IOP sensor.

Published
2017
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3. Biological aspects of axonal damage in glaucoma: A brief review

Author

Ernst R. Tamm, C. Ross Ethier, John E. Dowling, Crawford Downs, Mark H. Ellisman, Steven Fisher, Brad Fortune, Marcus Fruttiger, Tatjana Jakobs, Geoffrey Lewis, Richard H. Masland, Claire H. Mitchell, John Morrison, Sansar C. Sharma, Ian Sigal, Michael Sofroniew, Lin Wang, Janey Wiggs, and Samuel Wu

Subjects
0301 basic medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, Ophthalmology, 030104 developmental biology, 0302 clinical medicine, 030221 ophthalmology & optometry, Sensory Systems
Published
2017
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4. List of Contributors

Author

Anthony P Adamis, Grazyna Adamus, Daniel M Albert, Ann-Christin Albertsmeyer, Nishani Amerasinghe, Michael G Anderson, Sally S Atherton, Tin Aung, Rebecca S Bahn, David Sander Bardenstein, Neal P Barney, David C Beebe, Adrienne Berman, Audrey M Bernstein, Pooja Bhat, Douglas Borchman, Stephen Brocchini, Claude Burgoyne, Michelle Trager Cabrera, Richard J Cenedella, Jin-Hong Chang, Aimee Chappelow, Anuj Chauhan, Abbot F Clark, Ellen B Cook, Zélia M Corrêa, Scott Cousins, Gerald Cox, Scott Adam Croes, Karl G Csaky, Annegret Hella Dahlmann-Noor, Reza Dana, Helen Danesh-Meyer, Julie T Daniels, Darlene A Dartt, Mohammad H Dastjerdi, Nigel W Daw, Daniel G Dawson, Alejandra de Alba Campomanes, Joseph L Demer, Suzanne M Dintzis, J Crawford Downs, Henry Edelhauser, David Ellenberg, Victor Elner, Steven K Fisher, Robert Folberg, C Stephen Foster, Gary N Foulks, Frederick T Fraunfelder, Frederick W Fraunfelder, Anne Fulton, Ronald Gaster, Stylianos Georgoulas, Michael S Gilmore, Ilene K Gipson, Michaël J A Girard, Lynn K Gordon, Irene Gottlob, John D Gottsch, Frank M Graziano, Hans E Grossniklaus, Deborah Grzybowski, Clyde Guidry, Neeru Gupta, David H Gutmann, Vinay Gutti, John R Guy, J William Harbour, Mary Elizabeth Hartnett, Sohan S Hayreh, Susan Heimer, Robert Hess, Nancy M Holekamp, Suber S Huang, Sudha K Iyengar, Allen T Jackson, L Alan Johnson, Peter F Kador, Alon Kahana, Randy Kardon, Maria Cristina Kenney, Timothy Scott Kern, Peng Tee Khaw, Alice S Kim, Henry Klassen, Paul Knepper, Jane F Koretz, Mirunalini Kumaradas, Jonathan H Lass, David Lederer, Mark Lesk, Leonard A Levin, Geoffrey P Lewis, Zhuqing Li, Amy Lin, Robert A Linsenmeier, Robert Listernick, Martin Lubow, Andrew Maniotis, Pascale Massin, Katie Matatall, Russell L McCally, Stephen D McLeod, Muhammad Memon, Joan W Miller, Austin K Mircheff, Jay Neitz, Maureen Neitz, Christine C Nelson, Robert Nickells, Robert B Nussenblatt, Joan M O’Brien, Daniel T Organisciak, Michel Paques, Heather R Pelzel, Shamira Perera, Eric A Pierce, Jean Pournaras, Jonathan T Pribila, Frank A Proudlock, Xiaoping Qi, Narsing A Rao, Robert Ritch, Joseph F Rizzo, Michael D Roberts, James T Rosenbaum, Barry Rouse, Daniel R Saban, Alfredo A Sadun, Abbas K Samadi, Pranita Sarangi, Andrew P Schachat, Joel E Schechter, A Reagan Schiefer, Ursula Schlötzer-Schrehardt, Ingo Schmack, Leopold Schmetterer, Genevieve Aleta Secker, Srilakshmi M Sharma, James A Sharpe, Heather Sheardown, Alex Shortt, Ying-Bo Shui, Ian Sigal, James L Stahl, Roger F Steinert, Arun N E Sundaram, Janet S Sunness, Nathan T Tagg, Daniela Toffoli, Cynthia A Toth, Elias I Traboulsi, James C Tsai, Budd Tucker, Russell N Van Gelder, Hans Eberhard Völcker, Christopher S von Bartheld, Jianhua Wang, Judith West-Mays, Corey B Westerfeld, Steven E Wilson, Fabricio Witzel de Medeiros, Chih-Wei Wu, Ai Yamada, Steven Yeh, Thomas Yorio, Michael J Young, Terri L Young, Yeni H Yücel, Beatrice Y J T Yue, Marco A Zarbin, Xinyu Zhang, and Mei Zheng

Published
2010
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5. Mesh Morphing and Response Surface Analysis: Quantifying Sensitivity of Vertebral Mechanical Behavior.

Author

Ian Sigal and Cari Whyne

Abstract

Abstract  Vertebrae provide essential biomechanical stability to the skeleton. In this work novel morphing techniques were used to parameterize three aspects of the geometry of a specimen-specific finite element (FE) model of a rat caudal vertebra (process size, neck size, and end-plate offset). Material properties and loading were also parameterized using standard techniques. These parameterizations were then integrated within an RSM framework and used to produce a family of FE models. The mechanical behavior of each model was characterized by predictions of stress and strain. A metamodel was fit to each of the responses to yield the relative influences of the factors and their interactions. The direction of loading, offset, and neck size had the largest influences on the levels of vertebral stress and strain. Material type was influential on the strains, but not the stress. Process size was substantially less influential. A strong interaction was identified between dorsal–ventral offset and dorsal–ventral off-axis loading. The demonstrated approach has several advantages for spinal biomechanical analysis by enabling the examination of the sensitivity of a specimen to multiple variations in shape, and of the interactions between shape, material properties, and loading. [ABSTRACT FROM AUTHOR]

Published
2010
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