scholarly journals Inhibitor of Lysyl Oxidase in The Optic Nerve Head Complex Imparts Partial Protection Against Injury in Experimental Glaucoma

2021 ◽  
Author(s):  
Carlos M Cordoba ◽  
Magally Barrera ◽  
Sandra Perdomo ◽  
Pedro Gabriel Franco ◽  
Jaidy Acosta Alvarez ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Optic Nerve Head ◽  
Ganglion Cells ◽  
Lysyl Oxidase ◽  
Inflammatory Marker ◽  
Neurite Growth ◽  
Oxidase Inhibitor ◽  
Complement C3 ◽  
Marker Genes ◽  
Glial Fibrillary Acid Protein

Abstract Background: Glaucoma is a neurodegenerative disease with the progressive loss of retinal ganglion cells and changes in the optic nerve head (ONH). These changes are exacerbated by an increase in intraocular pressure (IOP). Methods: The effect of scleral and optic nerve softening with beta aminopropionitrile a lysyl oxidase inhibitor (BAPN) and stiffening with genipin, in a model of chronic increase of IOP was evaluated. Changes in optic nerve and retina were evaluated. H&E, Bielschowsky's silver staining and glial fibrillary acid protein (GFAP) staining was performed on optic nerve, retina and scleral structures. Changes in the expression of the Ywhab, Yhwaz (prosurvival genes), C3 complement (complement C3 inflammatory marker), CPG15 (neurite growth and neural survival gene) GFAP (glial activator marker) genes was carried out in the different groups.Results: Protective effect of BAPN was evident by the preservation of the optic nerve structure, and with the conservation of the retinal structures, while deleterious changes were evident in the stiffening of ONH complex, characterized by the increase in the glia, changes in the optic nerve, and disorganization in the retina. BAPN induced a reduction in the expression of Ywhab, Yhwaz (prosurvival genes), C3 and GFAP (inflammatory and glial marker) and CPG15. Conclusions: These findings support the critical involvement of changes in the ONH stiffness in the progression of glaucoma. The control of this variable as a regulatory mechanism in the progression of neural glaucomatous damage must be considered and would be explored as a possible intervention in glaucoma management.

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

scholarly journals Retinal hemorrhages as one of complications of optic disc drusen during pregnancy

2014 ◽  
Vol 67 (5-6) ◽  
pp. 185-189
Author(s):  
Marija Trenkic-Bozinovic ◽  
Predrag Jovanovic ◽  
Gordana Zlatanovic ◽  
Dragan Veselinovic ◽  
Aleksandra Aracki-Trenkic ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Optic Nerve ◽  
Visual Field ◽  
Optic Disc ◽  
Optic Nerve Head ◽  
Ganglion Cells ◽  
Therapeutic Interventions ◽  
Visual Field Defects ◽  
Retinal Hemorrhages ◽  
Optic Disc Drusen

Introduction. Drusen of the optic nerve head are relatively benign and asymptomatic. They represent retinal hyaline corpuscles resulting from impaired axoplasmic transport of the retinal ganglion cells of optic nerve in front of the lamina cribrosa. They are usually detected accidentally, during a routine ophthalmologic examination. Most patients with optic disc drusen are not aware of the deterioration of their eyesight because of the slow progression of visual field defects. Damage in visual acuity due to optic disc drusen is rare. Case Report. A 27-year-old female patient in the sixth month of pregnancy visited an ophthalmologist because of a visual impairment described as the appearance of mist and shadows over her right eye. When first examined, her visual acuity in both eyes was 20/20. The retinal hemorrhages framing the bottom half of the optic nerve were seen. Complete laboratory and clinical testing as well as specific ophthalmic examinations (photofundus, computerized visual field, optical coherence tomography, and ultrasound) were performed to exclude systemic causes and they presented no risk for the pregnancy. Echosonographic examination confirmed the presence of bilateral optic nerve head drusen. Conclusion. Hemodynamic changes during pregnancy are possible factors for the development of optical disc and retinal hemorrhages. Since treatment of optic disc drusen is limited, recognition of optic nerve drusen as a cause of hemorrhage during pregnancy prevents unnecessary diagnostic and therapeutic interventions.

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.

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].

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.

scholarly journals The Glial Design of a Teleost Optic Nerve Head Supporting Continuous Growth

2002 ◽  
Vol 50 (10) ◽  
pp. 1289-1302 ◽  
Author(s):  
Concepción Lillo ◽  
Almudena Velasco ◽  
David Jimeno ◽  
Elena Cid ◽  
Juan M. Lara ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Optic Nerve Head ◽  
Ganglion Cells ◽  
Müller Cells ◽  
Nuclear Antigen ◽  
Muller Cells ◽  
Continuous Growth ◽  
Dividing Cells ◽  
Regional Adaptation ◽  
Tench Tinca Tinca

This study demonstrates the peculiarities of the glial organization of the optic nerve head (ONH) of a fish, the tench ( Tinca tinca), by using immunohistochemistry and electron microscopy. We employed antibodies specific for the macroglial cells: glutamine synthetase (GS), glial fibrillary acidic protein (GFAP), and S100. We also used the N518 antibody to label the new ganglion cells' axons, which are continuously added to the fish retina, and the anti-proliferating cell nuclear antigen (PCNA) antibody to specifically locate dividing cells. We demonstrate a specific regional adaptation of the GS-S100-positive Müller cells' vitreal processes around the optic disc, strongly labeled with the anti-GFAP antibody. In direct contact with these Müller cells' vitreal processes, there are S100-positive astrocytes and S100-negative cells ultrastructurally identified as microglial cells. Moreover, a population of PCNA-positive cells, characterized as glioblasts, forms the limit between the retina and the optic nerve in a region homologous to the Kuhnt intermediary tissue of mammals. Finally, in the intraocular portion of the optic nerve there are differentiating oligodendrocytes arranged in rows. Both the glioblasts and the rows of developing cells could serve as a pool of glial elements for the continuous growth of the visual system.

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