The Experts below are selected from a list of 261 Experts worldwide ranked by ideXlab platform
James Edwards Morgan - One of the best experts on this subject based on the ideXlab platform.
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digestion of the glycosaminoglycan extraCellular matrix by chondroitinase abc supports retinal Ganglion Cell dendritic preservation in a rodent model of experimental glaucoma
Molecular Brain, 2018Co-Authors: James R. Tribble, Peter A. Williams, Bruce Caterson, Frank Sengpiel, James Edwards MorganAbstract:Retinal Ganglion Cell dendritic atrophy is an early feature of glaucoma, and the recovery of retinal Ganglion Cell dendrites is a viable option for vision improvement in glaucoma. Retinal Ganglion Cell neurites are surrounded by a specialised glycosaminoglycan extraCellular matrix which inhibits dendritic plasticity. Since digestion of the extraCellular matrix by chondroitinase ABC has been reported to have neuro-regenerative and neuro-plastic effects within the central nervous system, we explored its potential for dendritic recovery in a rat model of ocular hypertension. Chondroitinase ABC was administrated intravitreally 1 week after ocular hypertension (a time point where dendritic atrophy has already occurred). Retinal Ganglion Cell dendritic morphology was unaffected by chondroitinase ABC in normal retina. In ocular hypertensive eyes retinal Ganglion Cells showed significantly decreased dendritic length and area under the Sholl curve with atrophy confined to higher order dendrites. These changes were not observed in chondroitinase ABC injected eyes despite similar total retinal Ganglion Cell loss (i.e. dendritic protection of surviving retinal Ganglion Cells). These data suggest that glycosaminoglycan digestion could have a therapeutic role in mitigating the effects of elevated pressure on retinal Ganglion Cell dendritic structure in glaucoma.
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The optical detection of retinal Ganglion Cell damage
Eye, 2017Co-Authors: James Edwards Morgan, James R. Tribble, Nick White, James Fergusson, Irina ErchovaAbstract:We provide an overview of developments in the use OCT imaging for the detection of retinal Ganglion Cell damage in vivo that avoid use of any exogenous ligands to label Cells. The method employs high resolution OCT using broad spectral light sources to deliver axial resolution of under 5 microns. The resolution approximates that of Cellular organelles, which undergo degenerative changes that progress to apoptosis as a result of axon damage. These degenerative changes are manifest as the loss of retinal Ganglion Cell dendrites and fragmentation of the subCellular network of organelles, in particular, the mitochondria that support dendritic structure. These changes can alter the light scattering behaviour of degenerating neurons. Using OCT imaging techniques to identify these signals in cultured neurons, we have demonstrated changes in cultured Cells and in retinal explants. Pilot studies in human glaucoma suggest that similar changes are detectable in the clinical setting. High resolution OCT can be used to detect optical scatter signals that derive from the retinal Ganglion Cell layer and are associated with neuronal damage. These findings suggest that OCT instruments can be used to derive quantitative measurements of retinal Ganglion Cell damage. Critically, these signals can be detected at an early stage of retinal Ganglion Cell degeneration when Cells could be protected or remodeled to support visual recovery.
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Retinal Ganglion Cell Dendritic Atrophy in DBA/2J Glaucoma
PloS one, 2013Co-Authors: Peter A. Williams, Gareth R. Howell, Jessica M. Barbay, Catherine E. Braine, Gregory L. Sousa, Simon W. M. John, James Edwards MorganAbstract:Glaucoma is a complex disease affecting an estimated 70 million people worldwide, characterised by the progressive degeneration of retinal Ganglion Cells and accompanying visual field loss. The common site of damage to retinal Ganglion Cells is thought to be at the optic nerve head, however evidence from other optic neuropathies and neurodegenerative disorders suggests that dendritic structures undergo a prolonged period of atrophy that may accompany or even precede soma loss and neuronal Cell death. Using the DBA/2J mouse model of glaucoma this investigation aims to elucidate the impact of increasing intraocular pressure on retinal Ganglion Cell dendrites using DBA/2J mice that express YFP throughout the retinal Ganglion Cells driven by Thy1 (DBA/2J.Thy1(YFP)) and DiOlistically labelled retinal Ganglion Cells in DBA/2J mice. Here we show retinal Ganglion Cell dendritic degeneration in DiOlistically labelled DBA/2J retinal Ganglion Cells but not in the DBA/2J.Thy1(YFP) retinal Ganglion Cells suggesting that a potential downregulation of Thy1 allows only ‘healthy’ retinal Ganglion Cells to express YFP. These data may highlight alternative pathways to retinal Ganglion Cell loss in DBA/2J glaucoma.
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retina Ganglion Cell degeneration in glaucoma an opportunity missed a review
Clinical and Experimental Ophthalmology, 2012Co-Authors: James Edwards MorganAbstract:Retinal Ganglion Cell degeneration has been reported in a range of experimental models of glaucoma. Manifest as pruning of retinal Ganglion Cell dendrites, it is likely to influence both the function and viability of affected Cells. Electrophysiological studies in primate glaucoma have shown that affected Cells retain some function and could therefore form a neural substrate for the recovery of visual function in glaucoma. Clinical studies in which the intraocular pressure is reduced have suggested that some improvement in retinal function may be possible in hypotensive eyes. These experimental studies highlight the importance of establishing the extent to which retinal Ganglion Cell degeneration occurs in human glaucoma. If substantial numbers of degenerating retinal Ganglion Cells are present in glaucoma, they could present an ideal target for the recovery of vision.
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Retinal Ganglion Cell shrinkage in glaucoma.
Journal of glaucoma, 2002Co-Authors: James Edwards MorganAbstract:SUMMARY: There has been some debate concerning the selective loss of retinal Ganglion Cells belonging to the magnoCellular pathway in early glaucoma. Although histologic studies of retinal Ganglion Cells in experimental and human glaucoma have suggested selective loss of the larger Cells and, by implication, selective damage to the magnoCellular pathway, this has not been confirmed using psychophysical tests. Recent studies of retinal Ganglion Cell morphology in experimental glaucoma provide evidence that retinal Ganglion Cells undergo morphologic changes prior to Cell death; Cell volume is reduced in surviving Cells with corresponding reductions in the size of the axon and dendritic tree. The magnitude of these changes is consistent with Cell shrinkage as an explanation for the apparent selective damaged reported in earlier studies. It is also likely that widespread changes in the retinal Ganglion Cell population precede Cell death, which will affect the physiologic behavior of these Cells.
Robert W Nickells - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the percentage of Ganglion Cells in the Ganglion Cell layer of the rodent retina
Molecular Vision, 2013Co-Authors: Cassandra L Schlamp, Angela D Montgomery, Caitlin Mac E Nair, Claudia Schuart, Daniel J Willmer, Robert W NickellsAbstract:Purpose: Retinal Ganglion Cells comprise a percentage of the neurons actually residing in the Ganglion Cell layer (GCL) of the rodent retina. This estimate is useful to extrapolate Ganglion Cell loss in models of optic nerve disease, but the values reported in the literature are highly variable depending on the methods used to obtain them. Methods: We tested three retrograde labeling methods and two immunostaining methods to calculate Ganglion Cell number in the mouse retina (C57BL/6). Additionally, a double-stain retrograde staining method was used to label rats (Long-Evans). The number of total neurons was estimated using a nuclear stain and selecting for nuclei that met specific criteria. Cholinergic amacrine Cells were identified using transgenic mice expressing Tomato fluorescent protein. Total neurons and total Ganglion Cell numbers were measured in microscopic fields of 10 4 µm 2 to determine the percentage of neurons comprising Ganglion Cells in each field. Results: Historical estimates of the percentage of Ganglion Cells in the mouse GCL range from 36.1% to 67.5% depending on the method used. Experimentally, retrograde labeling methods yielded a combined estimate of 50.3% in mice. A retrograde method also yielded a value of 50.21% for rat retinas. Immunolabeling estimates were higher at 64.8%. Immunolabeling may introduce overestimates, however, with non-specific labeling effects, or ectopic expression of antigens in neurons other than Ganglion Cells. Conclusions: Since immunolabeling methods may overestimate Ganglion Cell numbers, we conclude that 50%, which is consistently derived from retrograde labeling methods, is a reliable estimate of the Ganglion Cells in the neuronal population of the GCL.
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Dominant inheritance of retinal Ganglion Cell resistance to optic nerve crush in mice
BMC Neuroscience, 2007Co-Authors: Yan Li, Sheila J Semaan, Cassandra L Schlamp, Robert W NickellsAbstract:Background Several neurodegenerative diseases are influenced by complex genetics that affect an individual's susceptibility, disease severity, and rate of progression. One such disease is glaucoma, a chronic neurodegenerative condition of the eye that targets and stimulates apoptosis of CNS neurons called retinal Ganglion Cells. Since Ganglion Cell death is intrinsic, it is reasonable that the genes that control this process may contribute to the complex genetics that affect Ganglion Cell susceptibility to disease. To determine if genetic background influences susceptibility to optic nerve damage, leading to Ganglion Cell death, we performed optic nerve crush on 15 different inbred lines of mice and measured Ganglion Cell loss. Resistant and susceptible strains were used in a reciprocal breeding strategy to examine the inheritance pattern of the resistance phenotype. Because earlier studies had implicated Bax as a susceptibility allele for Ganglion Cell death in the chronic neurodegenerative disease glaucoma, we conducted allelic segregation analysis and mRNA quantification to assess this gene as a candidate for the Cell death phenotype. Results Inbred lines showed varying levels of susceptibility to optic nerve crush. DBA/2J mice were most resistant and BALB/cByJ mice were most susceptible. F1 mice from these lines inherited the DBA/2J phenotype, while N2 backcross mice exhibited the BALB/cByJ phenotype. F2 mice exhibited an intermediate phenotype. A Wright Formula calculation suggested as few as 2 dominant loci were linked to the resistance phenotype, which was corroborated by a Punnett Square analysis of the distribution of the mean phenotype in each cross. The levels of latent Bax mRNA were the same in both lines, and Bax alleles did not segregate with phenotype in N2 and F2 mice. Conclusion Inbred mice show different levels of resistance to optic nerve crush. The resistance phenotype is heritable in a dominant fashion involving relatively few loci. Bax was excluded as a candidate gene for this phenotype.
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progressive Ganglion Cell loss and optic nerve degeneration in dba 2j mice is variable and asymmetric
BMC Neuroscience, 2006Co-Authors: Cassandra L Schlamp, Joel A Dietz, Katherine T Janssen, Robert W NickellsAbstract:Background Glaucoma is a chronic neurodegenerative disease of the retina, characterized by the degeneration of axons in the optic nerve and retinal Ganglion Cell apoptosis. DBA/2J inbred mice develop chronic hereditary glaucoma and are an important model system to study the molecular mechanisms underlying this disease and novel therapeutic interventions designed to attenuate the loss of retinal Ganglion Cells. Although the genetics of this disease in these mice are well characterized, the etiology of its progression, particularly with respect to retinal degeneration, is not. We have used two separate labeling techniques, post-mortem DiI labeling of axons and Ganglion Cell-specific expression of the βGeo reporter gene, to evaluate the time course of optic nerve degeneration and Ganglion Cell loss, respectively, in aging mice.
Harry A. Quigley - One of the best experts on this subject based on the ideXlab platform.
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retinal Ganglion Cell morphology after optic nerve crush and experimental glaucoma
Investigative Ophthalmology & Visual Science, 2012Co-Authors: G Kalesnykas, Ericka Oglesby, Matthew R. Steinhart, Mary Ellen Pease, Donald J Zack, Frances E Cone, Jing Tian, Harry A. QuigleyAbstract:Purpose. To study sequential changes in retinal Ganglion Cell (RGC) morphology in mice after optic nerve crush and after induction of experimental glaucoma.
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visual field defects and retinal Ganglion Cell losses in patients with glaucoma
Archives of Ophthalmology, 2006Co-Authors: Ronald S Harwerth, Harry A. QuigleyAbstract:Objective To determine whether the structure-function relationships for glaucoma in humans and experimental glaucoma in monkeys are similar. Methods The study was based on retinal Ganglion Cell density and visual thresholds in patients with documented glaucoma. Data were analyzed with a model that predicted Ganglion Cell density from standard clinical perimetry, which was then compared with histologic Cell counts. Results The model, without free parameters, produced accurate and relatively precise quantification of Ganglion Cell density associated with visual field defects. For 437 sets of data, the unity correlation for predicted vs measured Cell density had a coefficient of determination of 0.39. The mean absolute deviation of the predicted vs measured values was 2.59 decibels (dB), and the mean ± SD of the distribution of residual errors of prediction was −0.26 ± 3.22 dB. Conclusions Visual field defects based on standard clinical perimetry are proportional to neural losses caused by glaucoma. Clinical Relevance The evidence for quantitative structure-function relationships provides a scientific basis for interpreting glaucomatous neuropathy from visual thresholds and supports the application of standard perimetry to establish the stage of the disease.
Cassandra L Schlamp - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the percentage of Ganglion Cells in the Ganglion Cell layer of the rodent retina
Molecular Vision, 2013Co-Authors: Cassandra L Schlamp, Angela D Montgomery, Caitlin Mac E Nair, Claudia Schuart, Daniel J Willmer, Robert W NickellsAbstract:Purpose: Retinal Ganglion Cells comprise a percentage of the neurons actually residing in the Ganglion Cell layer (GCL) of the rodent retina. This estimate is useful to extrapolate Ganglion Cell loss in models of optic nerve disease, but the values reported in the literature are highly variable depending on the methods used to obtain them. Methods: We tested three retrograde labeling methods and two immunostaining methods to calculate Ganglion Cell number in the mouse retina (C57BL/6). Additionally, a double-stain retrograde staining method was used to label rats (Long-Evans). The number of total neurons was estimated using a nuclear stain and selecting for nuclei that met specific criteria. Cholinergic amacrine Cells were identified using transgenic mice expressing Tomato fluorescent protein. Total neurons and total Ganglion Cell numbers were measured in microscopic fields of 10 4 µm 2 to determine the percentage of neurons comprising Ganglion Cells in each field. Results: Historical estimates of the percentage of Ganglion Cells in the mouse GCL range from 36.1% to 67.5% depending on the method used. Experimentally, retrograde labeling methods yielded a combined estimate of 50.3% in mice. A retrograde method also yielded a value of 50.21% for rat retinas. Immunolabeling estimates were higher at 64.8%. Immunolabeling may introduce overestimates, however, with non-specific labeling effects, or ectopic expression of antigens in neurons other than Ganglion Cells. Conclusions: Since immunolabeling methods may overestimate Ganglion Cell numbers, we conclude that 50%, which is consistently derived from retrograde labeling methods, is a reliable estimate of the Ganglion Cells in the neuronal population of the GCL.
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Dominant inheritance of retinal Ganglion Cell resistance to optic nerve crush in mice
BMC Neuroscience, 2007Co-Authors: Yan Li, Sheila J Semaan, Cassandra L Schlamp, Robert W NickellsAbstract:Background Several neurodegenerative diseases are influenced by complex genetics that affect an individual's susceptibility, disease severity, and rate of progression. One such disease is glaucoma, a chronic neurodegenerative condition of the eye that targets and stimulates apoptosis of CNS neurons called retinal Ganglion Cells. Since Ganglion Cell death is intrinsic, it is reasonable that the genes that control this process may contribute to the complex genetics that affect Ganglion Cell susceptibility to disease. To determine if genetic background influences susceptibility to optic nerve damage, leading to Ganglion Cell death, we performed optic nerve crush on 15 different inbred lines of mice and measured Ganglion Cell loss. Resistant and susceptible strains were used in a reciprocal breeding strategy to examine the inheritance pattern of the resistance phenotype. Because earlier studies had implicated Bax as a susceptibility allele for Ganglion Cell death in the chronic neurodegenerative disease glaucoma, we conducted allelic segregation analysis and mRNA quantification to assess this gene as a candidate for the Cell death phenotype. Results Inbred lines showed varying levels of susceptibility to optic nerve crush. DBA/2J mice were most resistant and BALB/cByJ mice were most susceptible. F1 mice from these lines inherited the DBA/2J phenotype, while N2 backcross mice exhibited the BALB/cByJ phenotype. F2 mice exhibited an intermediate phenotype. A Wright Formula calculation suggested as few as 2 dominant loci were linked to the resistance phenotype, which was corroborated by a Punnett Square analysis of the distribution of the mean phenotype in each cross. The levels of latent Bax mRNA were the same in both lines, and Bax alleles did not segregate with phenotype in N2 and F2 mice. Conclusion Inbred mice show different levels of resistance to optic nerve crush. The resistance phenotype is heritable in a dominant fashion involving relatively few loci. Bax was excluded as a candidate gene for this phenotype.
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progressive Ganglion Cell loss and optic nerve degeneration in dba 2j mice is variable and asymmetric
BMC Neuroscience, 2006Co-Authors: Cassandra L Schlamp, Joel A Dietz, Katherine T Janssen, Robert W NickellsAbstract:Background Glaucoma is a chronic neurodegenerative disease of the retina, characterized by the degeneration of axons in the optic nerve and retinal Ganglion Cell apoptosis. DBA/2J inbred mice develop chronic hereditary glaucoma and are an important model system to study the molecular mechanisms underlying this disease and novel therapeutic interventions designed to attenuate the loss of retinal Ganglion Cells. Although the genetics of this disease in these mice are well characterized, the etiology of its progression, particularly with respect to retinal degeneration, is not. We have used two separate labeling techniques, post-mortem DiI labeling of axons and Ganglion Cell-specific expression of the βGeo reporter gene, to evaluate the time course of optic nerve degeneration and Ganglion Cell loss, respectively, in aging mice.
Ronald S Harwerth - One of the best experts on this subject based on the ideXlab platform.
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visual field defects and retinal Ganglion Cell losses in patients with glaucoma
Archives of Ophthalmology, 2006Co-Authors: Ronald S Harwerth, Harry A. QuigleyAbstract:Objective To determine whether the structure-function relationships for glaucoma in humans and experimental glaucoma in monkeys are similar. Methods The study was based on retinal Ganglion Cell density and visual thresholds in patients with documented glaucoma. Data were analyzed with a model that predicted Ganglion Cell density from standard clinical perimetry, which was then compared with histologic Cell counts. Results The model, without free parameters, produced accurate and relatively precise quantification of Ganglion Cell density associated with visual field defects. For 437 sets of data, the unity correlation for predicted vs measured Cell density had a coefficient of determination of 0.39. The mean absolute deviation of the predicted vs measured values was 2.59 decibels (dB), and the mean ± SD of the distribution of residual errors of prediction was −0.26 ± 3.22 dB. Conclusions Visual field defects based on standard clinical perimetry are proportional to neural losses caused by glaucoma. Clinical Relevance The evidence for quantitative structure-function relationships provides a scientific basis for interpreting glaucomatous neuropathy from visual thresholds and supports the application of standard perimetry to establish the stage of the disease.
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Ganglion Cell losses underlying visual field defects from experimental glaucoma
Investigative Ophthalmology & Visual Science, 1999Co-Authors: Ronald S Harwerth, Louvenia Carterdawson, Fran Shen, Earl L Smith, M L J CrawfordAbstract:PURPOSE. To investigate the relationship between Ganglion Cell losses and visual field defects caused by glaucoma. METHODS. Behavioral perimetry and histology data were obtained from 10 rhesus monkeys with unilateral experimental glaucoma that was induced by argon laser treatments to their trabecular meshwork. After significant visual field defects had developed, the retinas were collected for histologic analysis. The Ganglion Cells were counted by light microscopy in cresyl violet-stained retina sections, and the percentage of Ganglion Cell loss (treated to control eye counts) was compared with the depth of visual field defect (treated to control eye thresholds) at corresponding retinal and perimetry test locations. Sensitivity losses as a function of Ganglion Cell losses were analyzed for Goldmann III, white and Goldmann V, and short- and long-wavelength perimetry test stimuli. RESULTS. The relationship between the proportional losses of Ganglion Cells and visual sensitivity, measured with either white or colored stimuli, was nonlinear. With white stimuli, the visual sensitivity losses were relatively constant (approximately 6 dB) for Ganglion Cell losses of less than 30% to 50%, and then with greater amounts of Cell loss the visual defects were more systematically related to Ganglion Cell loss (approximately 0.42 dB/percent Cell loss). The forms of the neural-sensitivity relationships for visual defects measured with short- or long-wavelength perimetry stimuli were similar when the visual thresholds were normalized to compensate for differences in expected normal thresholds for white and colored perimetry stimuli. CONCLUSIONS. Current perimetry regimens with either white or monochromatic stimuli do not provide a useful estimate of Ganglion Cell loss until a substantial proportion have died. The variance in Ganglion Cell loss is large for mild defects that would be diagnostic of early glaucoma and for visual field locations near the fovea where sensitivity losses occur relatively late in the disease process. The neural-sensitivity relationships were essentially identical for both white and monochromatic test stimuli, and it therefore seems unlikely that the higher sensitivity for detecting glaucoma with monochromatic stimuli is based on the size-dependent susceptibility of Ganglion Cells to injury from glaucoma.
