The Experts below are selected from a list of 2424 Experts worldwide ranked by ideXlab platform
Dietmar Fischer - One of the best experts on this subject based on the ideXlab platform.
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boosting central nervous system axon regeneration by circumventing limitations of natural cytokine signaling
Molecular Therapy, 2016Co-Authors: Marco Leibinger, Anastasia Andreadaki, Philipp Gobrecht, Evgeny Levin, Heike Diekmann, Dietmar FischerAbstract:Retinal ganglion cells (RGCs) do not normally regenerate injured axons, but die upon axotomy. Although IL-6-like cytokines are reportedly neuroprotective and promote optic nerve regeneration, their overall regenerative effects remain rather moderate. Here, we hypothesized that direct activation of the gp130 receptor by the designer cytokine hyper-IL-6 (hIL-6) might induce stronger RGC regeneration than natural cytokines. Indeed, hIL-6 stimulated neurite growth of adult cultured RGCs with significantly higher efficacy than CNTF or IL-6. This neurite growth promoting effect could be attributed to stronger activation of the JAK/STAT3 and PI3K/AKT/mTOR signaling pathways and was also observed in peripheral dorsal root ganglion neurons. Moreover, hIL-6 abrogated axon growth inhibition by central nervous system (CNS) myelin. Remarkably, continuous hIL-6 expression upon RGC-specific AAV transduction after optic nerve crush exerted stronger axon regeneration than other known regeneration promoting treatments such as Lens Injury and PTEN knockout, with some axons growing through the optic chiasm 6 weeks after optic nerve Injury. Combination of hIL-6 with RGC-specific PTEN knockout further enhanced optic nerve regeneration. Therefore, direct activation of gp130 signaling might be a novel, clinically applicable approach for robust CNS repair.
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Lens Injury has a protective effect on photoreceptors in the rcs rat
International Scholarly Research Notices, 2013Co-Authors: Peter Heiduschka, Daniel Renninger, Dietmar Fischer, Sabine Hofmeister, Adrienne Muller, Ulrich SchraermeyerAbstract:Lens Injury induced activation of retinal glia, and subsequent release of ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF) potently protect axotomised retinal ganglion cells from apoptosis and promotes axon regeneration in the injured optic nerve. The goal of the current study was to investigate if similar effects may also be applicable to rescue photoreceptors from degeneration in a model of retinitis pigmentosa. Lens Injury was performed in the Royal College of Surgeons (RCS) rats at the age of one month. The survival of photoreceptors was evaluated histologically, and retinal function was analysed by electroretinography (ERG). Expression of CNTF was also analysed. Lens Injury significantly enhanced the survival of photoreceptors 1 month after surgery compared to untreated controls, which was associated with an enhanced ERG response. In addition, Lens Injury significantly protected photoreceptors from degeneration in the contralateral eye, although to a much lesser extent. We could show that Lens Injury is sufficient to transiently delay the degeneration of photoreceptors in the RCS rat. The observed neuroprotective effects may be at least partially mediated by an upregulation of CNTF expression seen after Lens Injury.
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Neuroprotective and Axon Growth-Promoting Effects following Inflammatory Stimulation on Mature Retinal Ganglion Cells in Mice Depend on Ciliary Neurotrophic Factor and Leukemia Inhibitory Factor
The Journal of Neuroscience, 2009Co-Authors: Marco Leibinger, Adrienne Muller, Thomas G Hauk, Anastasia Andreadaki, Matthias Kirsch, Dietmar FischerAbstract:After optic nerve Injury retinal ganglion cells (RGCs) normally fail to regenerate axons in the optic nerve and undergo apoptosis. However, Lens Injury (LI) or intravitreal application of zymosan switch RGCs into an active regenerative state, enabling these neurons to survive axotomy and to regenerate axons into the injured optic nerve. Several factors have been proposed to mediate the beneficial effects of LI. Here, we investigated the contribution of glial-derived ciliary neurotrophic factor (CNTF) to LI-mediated regeneration and neuroprotection using wild-type and CNTF-deficient mice. In wild-type mice, CNTF expression was strongly upregulated in retinal astrocytes, the JAK/STAT3 pathway was activated in RGCs, and RGCs were transformed into an active regenerative state after LI. Interestingly, retinal LIF expression was correlated with CNTF expression after LI. In CNTF-deficient mice, the neuroprotective and axon growth-promoting effects of LI were significantly reduced compared with wild-type animals, despite an observed compensatory upregulation of LIF expression in CNTF-deficient mice. The positive effects of LI and also zymosan were completely abolished in CNTF/LIF double knock-out mice, whereas LI-induced glial and macrophage activation was not compromised. In culture CNTF and LIF markedly stimulated neurite outgrowth of mature RGCs. These data confirm a key role for CNTF in directly mediating the neuroprotective and axon regenerative effects of inflammatory stimulation in the eye and identify LIF as an additional contributing factor.
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crystallins of the β γ superfamily mimic the effects of Lens Injury and promote axon regeneration
Molecular and Cellular Neuroscience, 2008Co-Authors: Dietmar Fischer, Adrienne Muller, Thomas G Hauk, Solon ThanosAbstract:Adult retinal ganglion cells (RGCs) can survive axotomy and regrow lengthy axons when exposed to Lens Injury (LI). The neuroprotective and axon-growth-promoting effects of LI have been attributed to an infiltration of activated macrophages into the inner eye and recently also to astrocyte-derived CNTF. The present work reveals that certain purified Lens proteins (crystallins) cause the effects of LI. Intravitreal injections of beta- or gamma-crystallins, but not of alpha-crystallin, strongly enhanced axon regeneration from retinal explants in culture, within peripheral nerve grafts or the crushed optic nerve. Deposition of the effective crystallins within the vitreous body was also associated with an influx of circulating macrophages and an activation of retinal astrocytes, Muller cells, and resident microglia. Furthermore beta-crystallin induced CNTF expression in retinal astrocytes and activation of CNTF's major downstream signaling pathway (JAK/STAT3) when intravitreally injected or added to the culture medium ex vivo. Consistently, in culture the addition of beta- and gamma-crystallins to the medium also increased axon regeneration from retinal explants. These results demonstrate that crystallins of the beta/gamma-superfamily are the Lens-derived activators of cascades, which lead to axonal regeneration and suggest that their effects might be mediated by astrocyte-derived CNTF.
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switching mature retinal ganglion cells to a robust growth state in vivo gene expression and synergy with rhoa inactivation
The Journal of Neuroscience, 2004Co-Authors: Dietmar Fischer, Victoria Petkova, Solon Thanos, Larry I BenowitzAbstract:The inability of mature CNS neurons to regenerate injured axons has been attributed to a loss of inherent growth potential of cells and to inhibitory signals associated with myelin and the glial scar. The present study investigated two complementary issues: (1) whether mature CNS neurons can be stimulated to alter their gene expression profile and switch into a strong growth state; and (2) whether inactivating RhoA, a convergence point for multiple inhibitory signals, is sufficient to produce strong regeneration even without activating the growth state of neurons. In the mature rat, retinal ganglion cells (RGCs) normally fail to regenerate axons through the injured optic nerve but can be stimulated to do so by activating macrophages in the eye (e.g., by Lens Injury). To investigate underlying changes in gene expression, we retrogradely labeled RGCs with a fluorescent dye, performed optic nerve surgery with or without Lens Injury, and 4 d later, dissociated retinas, isolated RGCs by fluorescence-activated cell sorting, and examined their profiles of gene expression using microarrays. To investigate the effects of inactivating RhoA, we transfected RGCs with adeno-associated viruses carrying a gene for C3 ribosyltransferase. Our results show that, with appropriate stimulation, mature CNS neurons can undergo dramatic changes in gene expression comparable with those seen in regenerating neurons of the PNS, and that RhoA inactivation by itself results in moderate regeneration, and strongly potentiates axon regeneration through the mature optic nerve when the growth state of neurons is activated.
Solon Thanos - One of the best experts on this subject based on the ideXlab platform.
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crystallins of the β γ superfamily mimic the effects of Lens Injury and promote axon regeneration
Molecular and Cellular Neuroscience, 2008Co-Authors: Dietmar Fischer, Adrienne Muller, Thomas G Hauk, Solon ThanosAbstract:Adult retinal ganglion cells (RGCs) can survive axotomy and regrow lengthy axons when exposed to Lens Injury (LI). The neuroprotective and axon-growth-promoting effects of LI have been attributed to an infiltration of activated macrophages into the inner eye and recently also to astrocyte-derived CNTF. The present work reveals that certain purified Lens proteins (crystallins) cause the effects of LI. Intravitreal injections of beta- or gamma-crystallins, but not of alpha-crystallin, strongly enhanced axon regeneration from retinal explants in culture, within peripheral nerve grafts or the crushed optic nerve. Deposition of the effective crystallins within the vitreous body was also associated with an influx of circulating macrophages and an activation of retinal astrocytes, Muller cells, and resident microglia. Furthermore beta-crystallin induced CNTF expression in retinal astrocytes and activation of CNTF's major downstream signaling pathway (JAK/STAT3) when intravitreally injected or added to the culture medium ex vivo. Consistently, in culture the addition of beta- and gamma-crystallins to the medium also increased axon regeneration from retinal explants. These results demonstrate that crystallins of the beta/gamma-superfamily are the Lens-derived activators of cascades, which lead to axonal regeneration and suggest that their effects might be mediated by astrocyte-derived CNTF.
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switching mature retinal ganglion cells to a robust growth state in vivo gene expression and synergy with rhoa inactivation
The Journal of Neuroscience, 2004Co-Authors: Dietmar Fischer, Victoria Petkova, Solon Thanos, Larry I BenowitzAbstract:The inability of mature CNS neurons to regenerate injured axons has been attributed to a loss of inherent growth potential of cells and to inhibitory signals associated with myelin and the glial scar. The present study investigated two complementary issues: (1) whether mature CNS neurons can be stimulated to alter their gene expression profile and switch into a strong growth state; and (2) whether inactivating RhoA, a convergence point for multiple inhibitory signals, is sufficient to produce strong regeneration even without activating the growth state of neurons. In the mature rat, retinal ganglion cells (RGCs) normally fail to regenerate axons through the injured optic nerve but can be stimulated to do so by activating macrophages in the eye (e.g., by Lens Injury). To investigate underlying changes in gene expression, we retrogradely labeled RGCs with a fluorescent dye, performed optic nerve surgery with or without Lens Injury, and 4 d later, dissociated retinas, isolated RGCs by fluorescence-activated cell sorting, and examined their profiles of gene expression using microarrays. To investigate the effects of inactivating RhoA, we transfected RGCs with adeno-associated viruses carrying a gene for C3 ribosyltransferase. Our results show that, with appropriate stimulation, mature CNS neurons can undergo dramatic changes in gene expression comparable with those seen in regenerating neurons of the PNS, and that RhoA inactivation by itself results in moderate regeneration, and strongly potentiates axon regeneration through the mature optic nerve when the growth state of neurons is activated.
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Lens Injury stimulated axonal regeneration throughout the optic pathway of adult rats
Experimental Neurology, 2001Co-Authors: Dietmar Fischer, Peter Heiduschka, Solon ThanosAbstract:Axonal regrowth and restoration of visual function were studied in adult rats. The optic nerve was completely cut behind the eye. The proximal and distal nerve stumps were realigned and the meninges sutured back together. During the same surgical procedure, the Lens was lesioned in order to induce secondary cellular cascades, which are known to strongly support the survival of retinal ganglion cells (RGCs) and to promote axonal regeneration. The anatomical and topographic restoration of the visual pathway was assessed neuroanatomically with the aid of anterograde and retrograde tracing using fluorescent dyes. It appeared that the axons formed growth cones at the junction of the suture soon after Injury, before glial cells and extracellular matrix proteins were able to cause local scar formation. Growth cones first entered the distal optic nerve stump 3 days after Injury, grew through it to reach the optic chiasm approximately 3 weeks after the lesion was made, and terminated within the retinoreceptive layers of the superior colliculus 5 weeks after lesioning. Quantification of the retrogradely labeled cell bodies within the regenerating retina revealed that up to 30% of the RGCs, which includes all major cell types, were capable of regenerating their axons along the entire visual pathway. To assess whether topography was restored, double-labeling experiments were performed, revealing only crude topographic restoration during the initial stages of regeneration. However, visual-evoked potentials could be recorded, indicating that synaptic transmission in higher visual areas was relatively intact. The data show, in principle, that cut axons can regenerate over long distances within the white matter of a central nerve like the adult optic nerve, spanning over 11 mm to the chiasm and between 12 and 15 mm to the thalamus and midbrain. The findings suggest, for the first time, that lentogenic stimulation of RGCs is sufficient to induce the formation of growth cones that can override inhibitors at the site of Injury, grow through the white matter of the optic nerve, pass through the optic chiasm, and make synaptic connections within the brain.
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cataractogenic Lens Injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture
Investigative Ophthalmology & Visual Science, 2000Co-Authors: Dietmar Fischer, Mitrofanis Pavlidis, Solon ThanosAbstract:METHODS. In adult albino rats, penetrating Lens Injury was performed by intraocular injection. To test for Injury-induced neuroprotective effects in vivo, fluorescence-prelabeled RGCs were axotomized by subsequent crush of the optic nerve (ON) with concomitant Lens Injury to cause cataract. The numbers of surviving RGCs were determined in retinal wholemounts and compared between the different experimental and control groups. To examine axonal regeneration in vivo, the ON was cut and replaced with an autologous piece of sciatic nerve (SN). Retinal ganglion cells with axons that had regenerated within the SN under Lens Injury or control conditions were retrogradely labeled with a fluorescent dye and counted on retinal wholemounts. Neurite regeneration was also studied in adult retinal explants obtained either after Lens Injury or without Injury. The numbers of axons were determined after 1 and 2 days in culture. Putative neurotrophins (NTs) were studied within immunohistochemistry and Western blot analysis. RESULTS. Cataractogenic Lens Injury performed at the same time as ON crush resulted in highly significant rescue of 746 6 126 RGCs/mm 2 (mean 6 SD; approximately 39% of total RGCs) 14 days after Injury compared with controls without Injury or with injection of buffer into the vitreous body (30 6 18 RGCs/mm 2 ). When Lens Injury was performed with a delay of 3 days after ON crush, 49% of RGCs survived, whereas delay of 5 days still rescued 45% of all RGCs. In the grafting paradigm virtually all surviving RGCs after Lens Injury appeared to have regenerated an axon within the SN graft (763 6 114 RGCs/mm 2 versus 79 6 17 RGCs/mm 2 in controls). This rate of regeneration corresponds to approximately 40% of all RGCs. In the regeneration paradigm in vitro preceding Lens Injury and ON crush 5 days previous resulted in a maximum of regeneration of 273 6 39 fibers/explant after 1 day and 574 6 38 fibers/explant after 2 days in vitro. In comparison, in control retinal pieces without Lens Injury 28 6 13 fibers/explant grew out at 1 day, and 97 6 37 fibers/explant grew out at 2 days in culture. Immunohistochemical and Western blot analysis of potential NTs in the injured Lens revealed no expression of ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), NT-4, nerve growth factor (NGF), and basic fibroblast growth factor (bFGF). CONCLUSIONS. The findings indicate that the Lens contains high neuroprotective and neuritogenic activity, which is not caused by NT. Compared with the data available in the literature, this neuroprotection is quantitatively among the highest ever reported within the adult rat visual system. (Invest Ophthalmol Vis Sci. 2000;41:3943‐3954)
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cataractogenic Lens Injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture
Investigative Ophthalmology & Visual Science, 2000Co-Authors: Dietmar Fischer, Mitrofanis Pavlidis, Solon ThanosAbstract:METHODS. In adult albino rats, penetrating Lens Injury was performed by intraocular injection. To test for Injury-induced neuroprotective effects in vivo, fluorescence-prelabeled RGCs were axotomized by subsequent crush of the optic nerve (ON) with concomitant Lens Injury to cause cataract. The numbers of surviving RGCs were determined in retinal wholemounts and compared between the different experimental and control groups. To examine axonal regeneration in vivo, the ON was cut and replaced with an autologous piece of sciatic nerve (SN). Retinal ganglion cells with axons that had regenerated within the SN under Lens Injury or control conditions were retrogradely labeled with a fluorescent dye and counted on retinal wholemounts. Neurite regeneration was also studied in adult retinal explants obtained either after Lens Injury or without Injury. The numbers of axons were determined after 1 and 2 days in culture. Putative neurotrophins (NTs) were studied within immunohistochemistry and Western blot analysis. RESULTS. Cataractogenic Lens Injury performed at the same time as ON crush resulted in highly significant rescue of 746 6 126 RGCs/mm 2 (mean 6 SD; approximately 39% of total RGCs) 14 days after Injury compared with controls without Injury or with injection of buffer into the vitreous body (30 6 18 RGCs/mm 2 ). When Lens Injury was performed with a delay of 3 days after ON crush, 49% of RGCs survived, whereas delay of 5 days still rescued 45% of all RGCs. In the grafting paradigm virtually all surviving RGCs after Lens Injury appeared to have regenerated an axon within the SN graft (763 6 114 RGCs/mm 2 versus 79 6 17 RGCs/mm 2 in controls). This rate of regeneration corresponds to approximately 40% of all RGCs. In the regeneration paradigm in vitro preceding Lens Injury and ON crush 5 days previous resulted in a maximum of regeneration of 273 6 39 fibers/explant after 1 day and 574 6 38 fibers/explant after 2 days in vitro. In comparison, in control retinal pieces without Lens Injury 28 6 13 fibers/explant grew out at 1 day, and 97 6 37 fibers/explant grew out at 2 days in culture. Immunohistochemical and Western blot analysis of potential NTs in the injured Lens revealed no expression of ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), NT-4, nerve growth factor (NGF), and basic fibroblast growth factor (bFGF). CONCLUSIONS. The findings indicate that the Lens contains high neuroprotective and neuritogenic activity, which is not caused by NT. Compared with the data available in the literature, this neuroprotection is quantitatively among the highest ever reported within the adult rat visual system. (Invest Ophthalmol Vis Sci. 2000;41:3943‐3954)
Barbara Lorber - One of the best experts on this subject based on the ideXlab platform.
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retinal ganglion cell survival and axon regeneration in wlds transgenic rats after optic nerve crush and Lens Injury
BMC Neuroscience, 2012Co-Authors: Barbara Lorber, Alessia Tassoni, Natalie D Bull, Marilita M Moschos, Keith R MartinAbstract:We have previously shown that the slow Wallerian degeneration mutation, whilst delaying axonal degeneration after optic nerve crush, does not protect retinal ganglion cell (RGC) bodies in adult rats. To test the effects of a combination approach protecting both axons and cell bodies we performed combined optic nerve crush and Lens Injury, which results in both enhanced RGC survival as well as axon regeneration past the lesion site in wildtype animals. As previously reported we found that the Wld S mutation does not protect RGC bodies after optic nerve crush alone. Surprisingly, we found that Wld S transgenic rats did not exhibit the enhanced RGC survival response after combined optic nerve crush and Lens Injury that was observed in wildtype rats. RGC axon regeneration past the optic nerve lesion site was, however, similar in Wld S and wildtypes. Furthermore, activation of retinal glia, previously shown to be associated with enhanced RGC survival and axon regeneration after optic nerve crush and Lens Injury, was unaffected in Wld S transgenic rats. RGC axon regeneration is similar between Wld S transgenic and wildtype rats, but Wld S transgenic rats do not exhibit enhanced RGC survival after combined optic nerve crush and Lens Injury suggesting that the neuroprotective effects of Lens Injury on RGC survival may be limited by the Wld S protein.
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Different factors promote axonal regeneration of adult rat retinal ganglion cells after Lens Injury and intravitreal peripheral nerve grafting
Journal of Neuroscience Research, 2008Co-Authors: Barbara Lorber, Martin Berry, Ann LoganAbstract:We have investigated the differential mediators of the neurotrophic effects of intravitreal peripheral nerve grafting and Lens Injury on adult rat retinal ganglion cells (RGC). Lens Injury and intravitreal peripheral nerve grafting both stimulated RGC neurite growth in vitro and axon regeneration past the optic nerve lesion site in vivo concomitant with activation of retinal glia and invasion of macrophages into the eye. These observations, together with the results of coculture studies using a macrophage-free intact peripheral nerve segment, a macrophage-free intact Lens, a macrophage-rich peripheral nerve segment, or a macrophage-rich injured Lens in retinal cultures suggest that the stimulation of RGC axon regeneration by Lens Injury and intravitreal peripheral nerve grafting share a common macrophage-derived component overlain by distinct Lens-derived and peripheral nerve-derived neurotrophic factors, respectively. RGC axon regeneration following Lens Injury and intravitreal peripheral nerve grafting was similar in vivo, correlating with similar retinal glia activation whereas, in vitro, the level of RGC neurite outgrowth was significantly higher following intravitreal peripheral nerve grafting compared with Lens Injury, concomitant with the presence of increased numbers of activated retinal glia. This suggests that in vivo RGC axon regeneration induced by Lens Injury and peripheral nerve grafting may be limited, in part, by factors derived from activated retinal glia.
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Lens Injury stimulates adult mouse retinal ganglion cell axon regeneration via both macrophage and Lens derived factors
European Journal of Neuroscience, 2005Co-Authors: Barbara Lorber, M Berry, Ann LoganAbstract:In the present study the effects of Lens Injury on retinal ganglion cell axon/neurite re-growth were investigated in adult mice. In vivo, Lens Injury promoted successful regeneration of retinal ganglion cell axons past the optic nerve lesion site, concomitant with the invasion of macrophages into the eye and the presence of activated retinal astrocytes/Muller cells. In vitro, retinal ganglion cells from Lens-lesioned mice grew significantly longer neurites than those from intact mice, which correlated with the presence of enhanced numbers of activated retinal astrocytes/Muller cells. Co-culture of retinal ganglion cells from intact mice with macrophage-rich lesioned Lens/vitreous body led to increased neurite lengths compared with co-culture with macrophage-free intact Lens/vitreous body, pointing to a neurotrophic effect of macrophages. Furthermore, retinal ganglion cells from mice that had no Lens Injury but had received intravitreal Zymosan injections to stimulate macrophage invasion into the eye grew significantly longer neurites compared with controls, as did retinal ganglion cells from intact mice co-cultured with macrophage-rich vitreous body from Zymosan-treated mice. The intact Lens, but not the intact vitreous body, exerted a neurotrophic effect on retinal ganglion cell neurite outgrowth, suggesting that Lens-derived neurotrophic factor(s) conspire with those derived from macrophages in Lens Injury-stimulated axon regeneration. Together, these results show that Lens Injury promotes retinal ganglion cell axon regeneration/neurite outgrowth in adult mice, an observation with important implications for axon regeneration studies in transgenic mouse models.
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Effects of LAR and PTP-BL phosphatase deficiency on adult mouse retinal cells activated by Lens Injury.
European Journal of Neuroscience, 2005Co-Authors: Barbara Lorber, Martin Berry, Wiljan Hendriks, Catharina E.e.m. Van Der Zee, Ann LoganAbstract:Using intact and Lens-lesioned wildtype, leucocyte common antigen-related phosphatase deficient (LARDeltaP) and protein tyrosine phosphatase (PTP)-BAS-like phosphatase deficient (PTP-BLDeltaP) mice, we have evaluated the role of LAR and PTP-BL in retinal ganglion cell survival and neuritogenesis, and survival of activated retinal glia in vitro. There were no differences in in vitro retinal ganglion cell neuritogenesis and survival, as well as in activated retinal glia survival between intact wildtype and intact LARDeltaP or PTP-BLDeltaP mutant mice. In wildtype, LARDeltaP, and PTP-BLDeltaP retinal cultures, pre-conditioning by Lens Injury significantly increased retinal ganglion cell neuritogenesis and activated retinal glia numbers. However, in retinal cultures from Lens-lesioned LARDeltaP and PTP-BLDeltaP mice, significantly smaller percentages of retinal ganglion cells grew neurites compared to Lens-lesioned wildtype cultures. Significantly increased numbers of retinal ganglion cells survived in retinal cultures from Lens-lesioned LARDeltaP mice compared to Lens-lesioned wildtypes. PTP-BL phosphatase deficiency did not affect retinal ganglion cell survival in retinal cultures from Lens-lesioned mice, though activated retinal glia numbers were significantly reduced in cultures from Lens-lesioned PTP-BLDeltaP mice compared to Lens-lesioned wildtypes. In summary, a functional phenotype was found in LARDeltaP and PTP-BLDeltaP mice, that was only obvious in Lens lesion-stimulated retinal cultures. These observations suggest that LAR enhances retinal ganglion cell neurite initiation whilst suppressing retinal ganglion cell survival, and that PTP-BL facilitates both retinal ganglion cell neurite initiation and survival of activated retinal glia.
Ann Logan - One of the best experts on this subject based on the ideXlab platform.
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Different factors promote axonal regeneration of adult rat retinal ganglion cells after Lens Injury and intravitreal peripheral nerve grafting
Journal of Neuroscience Research, 2008Co-Authors: Barbara Lorber, Martin Berry, Ann LoganAbstract:We have investigated the differential mediators of the neurotrophic effects of intravitreal peripheral nerve grafting and Lens Injury on adult rat retinal ganglion cells (RGC). Lens Injury and intravitreal peripheral nerve grafting both stimulated RGC neurite growth in vitro and axon regeneration past the optic nerve lesion site in vivo concomitant with activation of retinal glia and invasion of macrophages into the eye. These observations, together with the results of coculture studies using a macrophage-free intact peripheral nerve segment, a macrophage-free intact Lens, a macrophage-rich peripheral nerve segment, or a macrophage-rich injured Lens in retinal cultures suggest that the stimulation of RGC axon regeneration by Lens Injury and intravitreal peripheral nerve grafting share a common macrophage-derived component overlain by distinct Lens-derived and peripheral nerve-derived neurotrophic factors, respectively. RGC axon regeneration following Lens Injury and intravitreal peripheral nerve grafting was similar in vivo, correlating with similar retinal glia activation whereas, in vitro, the level of RGC neurite outgrowth was significantly higher following intravitreal peripheral nerve grafting compared with Lens Injury, concomitant with the presence of increased numbers of activated retinal glia. This suggests that in vivo RGC axon regeneration induced by Lens Injury and peripheral nerve grafting may be limited, in part, by factors derived from activated retinal glia.
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Lens Injury stimulates adult mouse retinal ganglion cell axon regeneration via both macrophage and Lens derived factors
European Journal of Neuroscience, 2005Co-Authors: Barbara Lorber, M Berry, Ann LoganAbstract:In the present study the effects of Lens Injury on retinal ganglion cell axon/neurite re-growth were investigated in adult mice. In vivo, Lens Injury promoted successful regeneration of retinal ganglion cell axons past the optic nerve lesion site, concomitant with the invasion of macrophages into the eye and the presence of activated retinal astrocytes/Muller cells. In vitro, retinal ganglion cells from Lens-lesioned mice grew significantly longer neurites than those from intact mice, which correlated with the presence of enhanced numbers of activated retinal astrocytes/Muller cells. Co-culture of retinal ganglion cells from intact mice with macrophage-rich lesioned Lens/vitreous body led to increased neurite lengths compared with co-culture with macrophage-free intact Lens/vitreous body, pointing to a neurotrophic effect of macrophages. Furthermore, retinal ganglion cells from mice that had no Lens Injury but had received intravitreal Zymosan injections to stimulate macrophage invasion into the eye grew significantly longer neurites compared with controls, as did retinal ganglion cells from intact mice co-cultured with macrophage-rich vitreous body from Zymosan-treated mice. The intact Lens, but not the intact vitreous body, exerted a neurotrophic effect on retinal ganglion cell neurite outgrowth, suggesting that Lens-derived neurotrophic factor(s) conspire with those derived from macrophages in Lens Injury-stimulated axon regeneration. Together, these results show that Lens Injury promotes retinal ganglion cell axon regeneration/neurite outgrowth in adult mice, an observation with important implications for axon regeneration studies in transgenic mouse models.
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Effects of LAR and PTP-BL phosphatase deficiency on adult mouse retinal cells activated by Lens Injury.
European Journal of Neuroscience, 2005Co-Authors: Barbara Lorber, Martin Berry, Wiljan Hendriks, Catharina E.e.m. Van Der Zee, Ann LoganAbstract:Using intact and Lens-lesioned wildtype, leucocyte common antigen-related phosphatase deficient (LARDeltaP) and protein tyrosine phosphatase (PTP)-BAS-like phosphatase deficient (PTP-BLDeltaP) mice, we have evaluated the role of LAR and PTP-BL in retinal ganglion cell survival and neuritogenesis, and survival of activated retinal glia in vitro. There were no differences in in vitro retinal ganglion cell neuritogenesis and survival, as well as in activated retinal glia survival between intact wildtype and intact LARDeltaP or PTP-BLDeltaP mutant mice. In wildtype, LARDeltaP, and PTP-BLDeltaP retinal cultures, pre-conditioning by Lens Injury significantly increased retinal ganglion cell neuritogenesis and activated retinal glia numbers. However, in retinal cultures from Lens-lesioned LARDeltaP and PTP-BLDeltaP mice, significantly smaller percentages of retinal ganglion cells grew neurites compared to Lens-lesioned wildtype cultures. Significantly increased numbers of retinal ganglion cells survived in retinal cultures from Lens-lesioned LARDeltaP mice compared to Lens-lesioned wildtypes. PTP-BL phosphatase deficiency did not affect retinal ganglion cell survival in retinal cultures from Lens-lesioned mice, though activated retinal glia numbers were significantly reduced in cultures from Lens-lesioned PTP-BLDeltaP mice compared to Lens-lesioned wildtypes. In summary, a functional phenotype was found in LARDeltaP and PTP-BLDeltaP mice, that was only obvious in Lens lesion-stimulated retinal cultures. These observations suggest that LAR enhances retinal ganglion cell neurite initiation whilst suppressing retinal ganglion cell survival, and that PTP-BL facilitates both retinal ganglion cell neurite initiation and survival of activated retinal glia.
Ferenc Kuhn - One of the best experts on this subject based on the ideXlab platform.
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glaucoma after ocular contusion a cohort study of the united states eye Injury registry
Journal of Glaucoma, 2005Co-Authors: Christopher A Girkin, Gerald Mcgwin, Robert Morris, Cherie Long, Ferenc KuhnAbstract:Purpose This cohort study was designed to evaluate risk factors for the development of posttraumatic glaucoma after ocular contusion. Methods Data from the United States Eye Injury Registry (USEIR) were obtained from a total of 6021 patients who experienced blunt ocular contusion. Logistic regression was used to evaluate the association between these baseline structural and functional ocular characteristics and posttraumatic glaucoma. Odds ratios with 95% confidence intervals were obtained. Results The 6-month incidence of developing posttraumatic glaucoma was 3.39%. The development of glaucoma was independently associated with: advancing age (OR = 1.02; 95% CI = 1.02, 1.03), visual acuity worse than 20/200 (OR = 1.92; 95% CI = 1.19, 3.10), iris Injury (OR = 1.60; 95% CI = 1.05, 2.44), Lens Injury (OR = 1.86; 95% CI = 1.11, 3.11), hyphema (OR = 2.23; 95% CI = 1.40, 3.54), or angle recession (OR = 1.71; 95% CI = 1.00, 2.90). Conclusion This study provides an estimate for the risk of developing glaucoma after ocular contusion in a large cohort of patients and has determined several independently predictive factors that were significantly associated with the development of posttraumatic glaucoma including poor initial visual acuity, advancing age, Lens Injury, angle recession, and hyphema.
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glaucoma following penetrating ocular trauma a cohort study of the united states eye Injury registry
American Journal of Ophthalmology, 2005Co-Authors: Christopher A Girkin, Gerald Mcgwin, Robert Morris, Ferenc KuhnAbstract:Purpose To evaluate associations between baseline structural and functional ocular characteristics and the risk of developing posttraumatic glaucoma after penetrating ocular Injury. Design Prospective cohort study Methods Data from the United States Eye Injury Registry (USEIR) were obtained from a total of 3,627 patients who experienced penetrating ocular Injury. The risk of posttraumatic glaucoma and associated structural and functional ocular risk factors was estimated. Results The risk of developing posttraumatic glaucoma was 2.67%. The development of glaucoma was independently associated with several baseline characteristics including advancing age (relative risk 1.02/yr 95% confidence interval [1.00, 1.03]), Lens Injury (1.56 [1.03, 2.35]), poor baseline visual acuity (2.59 [1.62, 4.14]), and inflammation (3.02 [1.52, 6.02]). Conclusions This study provides an estimate for the risk of developing glaucoma after penetrating ocular Injury in a large cohort of patients and determined several factors that are significantly associated with the development of post-traumatic glaucoma, including advancing age, Lens Injury, poor visual acuity, and intraocular inflammation.