Article
Biochemistry & Molecular Biology
Casey J. Keuthan, Julie A. Schaub, Meihan Wei, Weixiang Fang, Sarah Quillen, Elizabeth Kimball, Thomas V. Johnson, Hongkai Ji, Donald J. Zack, Harry A. Quigley
Summary: The level of intraocular pressure (IOP) is a major risk factor for glaucomatous optic neuropathy. This study found that the unmyelinated optic nerve region is differentially susceptible to IOP-induced damage compared to the myelinated region. Gene expression patterns in the unmyelinated optic nerve showed significant differences compared to the myelinated optic nerve and retina. Changes in gene expression induced by optic nerve injury were more extensive in the myelinated region than the unmyelinated region.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Andrea E. Dillinger, Gregor R. Weber, Matthias Mayer, Magdalena Schneider, Corinna Goeppner, Andreas Ohlmann, Mikhail Shamonin, Gareth J. Monkman, Rudolf Fuchshofer
Summary: Primary open-angle glaucoma is a neurodegenerative disease that is associated with structural changes in the optic nerve head and extracellular matrix. The molecular factors involved in this remodeling process, particularly TGF-beta 2 and CCN2/CTGF, play important roles in the pathogenesis of the disease. Understanding the function of CCN2/CTGF in normal and pathological conditions could provide insights into the development of new therapeutic approaches for glaucoma.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Ophthalmology
Priya Chaudhary, Cheri Stowell, Juan Reynaud, Stuart K. Gardiner, Hongli Yang, Galen Williams, Imee Williams, Nicholas Marsh-Armstrong, Claude F. Burgoyne
Summary: This study aimed to investigate the alterations of several proteins in the optic nerve head in non-human primate early/moderate experimental glaucoma. The findings suggest that early retrolaminar myelin disruption, accompanied by decreases in astrocyte process labeling and increases in microglial/macrophage density, occurs in this glaucoma model.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Ophthalmology
Mona Safizadeh, Amirreza Shaabani, Alireza Kamalipour, Masoud Aghsaei Fard, Kaileen Yeh, Mehdi Yaseri, Nikoo Hamzeh, Nassim Khatibi, Harsha Laxmana Rao, Robert Weinreb, Sasan Moghimi
Summary: OCTA can be used to detect reduced capillary density in fellow eyes of PXG patients, enabling earlier detection of glaucomatous loss in pseudoexfoliation disease and enhancing disease management.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Ophthalmology
Jing Zhao, Graydon Gonsalvez, Manuela Bartoli, Barbara A. Mysona, Sylvia B. Smith, Kathryn E. Bollinger
Summary: The study evaluated the ability of S1R to modulate reactivity responses of optic nerve head astrocytes (ONHAs) and found that S1R activation enhanced ONHA reactivity characteristics, which may have important implications for the survival of retinal ganglion cells.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Ophthalmology
Thanadet Chuangsuwanich, Tin A. Tun, Fabian A. Braeu, Xiaofei Wang, Zhi Yun Chin, Satish K. Panda, Martin Buist, Dan Milea, Nicholas Strouthidis, Shamira Perera, Monisha Esther Nongpiur, Tin Aung, Michael J. A. Girard
Summary: This study aimed to assess the strains in optic nerve head (ONH) induced by intraocular pressure (IOP) and gaze in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). The results showed that NTG subjects experienced higher strains due to gaze, while HTG subjects experienced higher strain due to IOP elevation, and these differences were most pronounced in the lamina cribrosa (LC) tissue.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Biophysics
Yik Tung Tracy Ling, Arina Korneva, Harry A. A. Quigley, Thao D. D. Nguyen
Summary: This study developed a computational modeling method to estimate the mechanical response of retinal ganglion cell axons in the optic nerve head under intraocular pressure. The results showed that astrocytic processes experienced higher strains than axonal compartments, but lower stresses. The size, alignment, and local area fraction of axonal compartments significantly affected the strain outcomes.
BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
(2023)
Article
Neurosciences
Carola Rutigliani, James R. Tribble, Anna Hagstrom, Emma Lardner, Gauti Johannesson, Gustav Stalhammar, Pete A. Williams
Summary: Neuroinflammation is a crucial component of neurodegenerative diseases. The evidence for neuroinflammation in glaucoma patients is limited. By utilizing well-preserved wax embedded eyes, we confirmed the presence of significant neuroinflammatory responses in the retina and optic nerve head of glaucoma patients.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Neurosciences
Arpan G. Mazumder, Amelie M. Jule, Daniel Sun
Summary: The reactive response of optic nerve head astrocytes in glaucoma remains poorly understood. This study found that astrocytes in the optic nerve exhibited a region-specific and temporally distinct response to elevated intraocular pressure (IOP). Energy metabolism, particularly oxidative phosphorylation and mitochondrial protein translation, played a crucial role in the response of optic nerve astrocytes to elevated IOP. The study also revealed limited neuroinflammation in the reactive response of optic nerve astrocytes.
MOLECULAR NEURODEGENERATION
(2023)
Article
Cell Biology
Ying Zhu, Rui Wang, Anthony C. Pappas, Philip Seifert, Andrej Savol, Ruslan I. Sadreyev, Daniel Sun, Tatjana C. Jakobs
Summary: The optic nerve head is believed to be the initial site of retinal ganglion cell injury in glaucoma. Astrocytes in the optic nerve head respond to injury by undergoing characteristic changes in cell morphology and gene expression profile. Increased intraocular pressure leads to upregulation of astrocytic phagocytosis, indicating its involvement in the early stages of glaucoma.
Review
Ophthalmology
Ramanjit Sihota, Talvir Sidhu, Tanuj Dada
Summary: Clinical examination of the optic nerve head is crucial for the screening, diagnosis, staging, and management of glaucoma. It is especially valuable in cases where imaging cannot identify specific abnormalities, providing a more accurate diagnosis.
CURRENT OPINION IN OPHTHALMOLOGY
(2021)
Article
Ophthalmology
Ji-Ah Kim, Eun Ji Lee, Tae-Woo Kim, Hee Kyung Yang, Jeong-Min Hwang
Summary: The microvasculature of the optic nerve head and peripapillary tissues in eyes with normal-tension glaucoma (NTG) and nonarteritic anterior ischemic optic neuropathy (NAION) was compared using optical coherence tomography angiography (OCTA). Despite similar levels of retinal nerve fiber layer loss and vessel density decreases in the peripapillary retina, there were differences in vessel densities in the optic nerve head between NTG and NAION eyes, suggesting distinct mechanisms of vascular impairment and optic nerve head damage in each condition.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Ophthalmology
Eugene A. Lowry, Steven L. Mansberger, Stuart K. Gardiner, Hongli Yang, Facundo Sanchez, Juan Reynaud, Shaban Demirel, Claude F. Burgoyne, Brad Fortune
Summary: The frequency and severity of optic nerve head prelaminar schisis were found to be greater in glaucoma and glaucoma suspect eyes compared to healthy control eyes, and were associated with markers of glaucoma severity.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2021)
Article
Neurosciences
Nathaniel Pappenhagen, Eric Yin, Autumn B. Morgan, Charles C. Kiehlbauch, Denise M. Inman
Summary: This study investigated the metabolic changes in optic nerve head astrocytes and found significant differences in glycolytic and respiratory activity between stretched and control cells. Stretched optic nerve head astrocytes showed increased dependency on glutamine, suggesting the need for NAD + replenishment for sustained glycolysis and provision of carbon for TCA cycle intermediates.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Emma K. Geiduschek, Colleen M. Mcdowell
Summary: Glaucoma is a progressive disease that leads to irreversible blindness. Understanding the cellular mechanisms behind optic nerve head damage during disease progression can help identify new drug targets and therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Ophthalmology
Amanda Chow, Liam McCrea, Elizabeth Kimball, Julie Schaub, Harry Quigley, Ian Pitha
EXPERIMENTAL EYE RESEARCH
(2020)
Letter
Ophthalmology
Arina Korneva, Julie Schaub, Joan Jefferys Erys, Elizabeth Kimball, Mary Pease, Manasi Nawathe, Thomas V. Johnson, Ian Pitha, Harry Quigley
EXPERIMENTAL EYE RESEARCH
(2020)
Article
Ophthalmology
Arina Korneva, Julie Schaub, Joan Jefferys, Elizabeth Kimball, Mary Ellen Pease, Manasi Nawathe, Thomas Johnson, Ian Pitha, Harry Quigley
EXPERIMENTAL EYE RESEARCH
(2020)
Article
Multidisciplinary Sciences
Sarah Quillen, Julie Schaub, Harry Quigley, Mary Pease, Arina Korneva, Elizabeth Kimball
Article
Pharmacology & Pharmacy
Henry T. Hsueh, Yoo-Chun Kim, Ian Pitha, Matthew D. Shin, Cynthia A. Berlinicke, Renee Ti Chou, Elizabeth Kimball, Julie Schaub, Sarah Quillen, Kirby T. Leo, Hyounkoo Han, Amy Xiao, Youngwook Kim, Matthew Appell, Usha Rai, HyeYoung Kwon, Patricia Kolodziejski, Laolu Ogunnaike, Nicole M. Anders, Avelina Hemingway, Joan L. Jefferys, Abhijit A. Date, Charles Eberhart, Thomas Johnson, Harry A. Quigley, Donald J. Zack, Justin Hanes, Laura M. Ensign
Summary: Glaucoma is the leading cause of irreversible blindness worldwide, with elevated intraocular pressure being a major risk factor. While current pharmaceutical interventions focus on lowering IOP, the progression of retinal ganglion cell degeneration may continue. This study explores a novel ion complexation approach for formulating microcrystals containing a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection, providing sustained therapeutic effects.
Article
Engineering, Biomedical
Arina Korneva, Elizabeth C. Kimball, Sarah Quillen, Joan L. Jefferys, Manasi Nawathe, Yik Tung Tracy Ling, Thao D. Nguyen, Harry A. Quigley
Summary: Understanding the responses of astrocytes in the optic nerve head to mechanical and biochemical stimuli is crucial for studying retinal ganglion cell axon degeneration in glaucoma. In a mouse model, elevated intraocular pressure caused alterations in the junctions between astrocytic processes and the peripapillary sclera, leading to increased structural compliance of the optic nerve head. Experimental treatment with TrypLE enzyme partially reproduced these alterations, suggesting the significance of astrocyte-sclera junction separation in increasing ONH compliance.
ACTA BIOMATERIALIA
(2023)
Article
Multidisciplinary Sciences
Elizabeth C. Kimball, Sarah Quillen, Mary E. Pease, Casey Keuthan, Aru Nagalingam, Donald J. Zack, Thomas Johnson, Harry A. Quigley
Summary: Aquaporin 4 is not found in astrocytes in the rodent optic nerve head, despite being highly expressed in the retina and myelinated optic nerve.
Article
Biochemistry & Molecular Biology
Casey J. Keuthan, Julie A. Schaub, Meihan Wei, Weixiang Fang, Sarah Quillen, Elizabeth Kimball, Thomas V. Johnson, Hongkai Ji, Donald J. Zack, Harry A. Quigley
Summary: The level of intraocular pressure (IOP) is a major risk factor for glaucomatous optic neuropathy. This study found that the unmyelinated optic nerve region is differentially susceptible to IOP-induced damage compared to the myelinated region. Gene expression patterns in the unmyelinated optic nerve showed significant differences compared to the myelinated optic nerve and retina. Changes in gene expression induced by optic nerve injury were more extensive in the myelinated region than the unmyelinated region.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Ophthalmology
Carolyn Guan, Mary Ellen Pease, Sarah Quillen, Yik Tung Tracy Ling, Ximin Li, Elizabeth Kimball, Thomas Johnson, Thao D. Nguyen, Harry A. Quigley
Summary: This study quantitatively measured the changes in lamina cribrosa cell and connective tissue structure in human glaucoma eyes. The results showed that in the pores of the lamina cribrosa, the proportionate area of both GFAP and F-actin processes was significantly lower in glaucoma eyes compared to controls, and the nuclei in glaucoma specimens were rounder. Furthermore, wider F-actin process width, narrower average lamina cribrosa beam width, and increased nuclear count per square millimeter were associated with worse glaucoma damage.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Ophthalmology
Yik Tung Tracy Ling, Mary E. Pease, Joan L. Jefferys, Elizabeth C. Kimball, Harry A. Quigley, Thao D. Nguyen
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)