The Experts below are selected from a list of 3747 Experts worldwide ranked by ideXlab platform
Barbara Lorber - One of the best experts on this subject based on the ideXlab platform.
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Retinal Glia promote dorsal root ganglion axon regeneration.
PLOS ONE, 2015Co-Authors: Barbara Lorber, James W. Fawcett, Daniel J. Chew, Stefanie M. Hauck, Rachel S. Chong, Keith R. MartinAbstract:Axon regeneration in the adult central nervous system (CNS) is limited by several factors including a lack of neurotrophic support. Recent studies have shown that Glia from the adult rat CNS, specifically Retinal astrocytes and Muller Glia, can promote regeneration of Retinal ganglion cell axons. In the present study we investigated whether Retinal Glia also exert a growth promoting effect outside the visual system. We found that Retinal Glial conditioned medium significantly enhanced neurite growth and branching of adult rat dorsal root ganglion neurons (DRG) in culture. Furthermore, transplantation of Retinal Glia significantly enhanced regeneration of DRG axons past the dorsal root entry zone after root crush in adult rats. To identify the factors that mediate the growth promoting effects of Retinal Glia, mass spectrometric analysis of Retinal Glial conditioned medium was performed. Apolipoprotein E and secreted protein acidic and rich in cysteine (SPARC) were found to be present in high abundance, a finding further confirmed by western blotting. Inhibition of Apolipoprotein E and SPARC significantly reduced the neuritogenic effects of Retinal Glial conditioned medium on DRG in culture, suggesting that Apolipoprotein E and SPARC are the major mediators of this regenerative response.
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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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Activated Retinal Glia mediated axon regeneration in experimental glaucoma.
Neurobiology of Disease, 2012Co-Authors: Barbara Lorber, Alessandra Guidi, James W. Fawcett, Keith R. MartinAbstract:Abstract Glaucoma, a leading cause of blindness, is a neurodegenerative disease characterized by progressive loss of Retinal ganglion cell axons in the optic nerve and their cell bodies in the retina. Reactive Retinal Glial changes have been observed in glaucoma but the role of such Glial changes in the pathogenesis of the condition remains unclear. In the present study we found that Retinal ganglion cells in an experimental animal model of glaucoma have an increased axon regenerative potential. Regeneration of adult rat Retinal ganglion cell axons after optic nerve crush was significantly increased in vivo when combined with intraocular pressure-induced experimental glaucoma. This enhanced axon regeneration response was correlated with a significant increase in activation of Glial fibrillary acidic protein + Retinal Glia. Using a dissociated Retinal ganglion cell culture model we showed that reducing the number of activated Retinal Glia with a Glial specific toxin, α-Aminoadipic acid, significantly reduced the growth potential of Retinal ganglion cells from glaucomatous rat eyes, suggesting that activated Retinal Glia mediate, at least in part, the growth promoting effect. This was shown to be mediated by both membrane-bound and soluble Glial-derived factors. Neurotrophin and ciliary neurotrophic/leukemia inhibitory factor blockers did not affect the regenerative potential, excluding these growth factors as principal mediators of the enhanced growth response occurring in glaucomatous Retinal cultures. These observations are the first to reveal that Retinal ganglion cells from glaucomatous rat eyes have an enhanced regenerative capacity. Furthermore, our results suggest that activated Retinal Glia mediate at least part of this response. Further work to understand and enhance the regeneration-promoting effect of activated Retinal Glia is required to determine if this approach could be useful as part of a therapeutic strategy to encourage optic nerve regeneration in glaucoma.
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Activated Retinal Glia promote neurite outgrowth of Retinal ganglion cells via apolipoprotein E.
Journal of Neuroscience Research, 2009Co-Authors: Barbara Lorber, Martin Berry, Michael R. Douglas, Toru Nakazawa, Ann LoganAbstract:In the present study, we investigated the role and mechanism through which activated Retinal Glia stimulate Retinal ganglion cell (RGC) neurite outgrowth. We have found that the level of Retinal Glial activation correlates directly with enhanced RGC neurite outgrowth after a preconditioning intravitreal Zymosan injection. Reduction in the number of activated Glia in primary rat Retinal cultures led to significantly reduced RGC neurite outgrowth. Glial-related neurite outgrowth appears to be, at least in part, mediated via apolipoprotein E (ApoE), which is expressed by activated Retinal astrocytes and Muller Glia. ApoE-deficient mice showed significantly reduced RGC neurite outgrowth potential after intravitreal Zymosan injection compared with age-matched wild-type animals. These observations suggest that ApoE, expressed by activated Retinal Glia, stimulates RGC neurite outgrowth after intravitreal Zymosan injection.
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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.
Keith R. Martin - One of the best experts on this subject based on the ideXlab platform.
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Retinal Glia promote dorsal root ganglion axon regeneration.
PLOS ONE, 2015Co-Authors: Barbara Lorber, James W. Fawcett, Daniel J. Chew, Stefanie M. Hauck, Rachel S. Chong, Keith R. MartinAbstract:Axon regeneration in the adult central nervous system (CNS) is limited by several factors including a lack of neurotrophic support. Recent studies have shown that Glia from the adult rat CNS, specifically Retinal astrocytes and Muller Glia, can promote regeneration of Retinal ganglion cell axons. In the present study we investigated whether Retinal Glia also exert a growth promoting effect outside the visual system. We found that Retinal Glial conditioned medium significantly enhanced neurite growth and branching of adult rat dorsal root ganglion neurons (DRG) in culture. Furthermore, transplantation of Retinal Glia significantly enhanced regeneration of DRG axons past the dorsal root entry zone after root crush in adult rats. To identify the factors that mediate the growth promoting effects of Retinal Glia, mass spectrometric analysis of Retinal Glial conditioned medium was performed. Apolipoprotein E and secreted protein acidic and rich in cysteine (SPARC) were found to be present in high abundance, a finding further confirmed by western blotting. Inhibition of Apolipoprotein E and SPARC significantly reduced the neuritogenic effects of Retinal Glial conditioned medium on DRG in culture, suggesting that Apolipoprotein E and SPARC are the major mediators of this regenerative response.
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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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Activated Retinal Glia mediated axon regeneration in experimental glaucoma.
Neurobiology of Disease, 2012Co-Authors: Barbara Lorber, Alessandra Guidi, James W. Fawcett, Keith R. MartinAbstract:Abstract Glaucoma, a leading cause of blindness, is a neurodegenerative disease characterized by progressive loss of Retinal ganglion cell axons in the optic nerve and their cell bodies in the retina. Reactive Retinal Glial changes have been observed in glaucoma but the role of such Glial changes in the pathogenesis of the condition remains unclear. In the present study we found that Retinal ganglion cells in an experimental animal model of glaucoma have an increased axon regenerative potential. Regeneration of adult rat Retinal ganglion cell axons after optic nerve crush was significantly increased in vivo when combined with intraocular pressure-induced experimental glaucoma. This enhanced axon regeneration response was correlated with a significant increase in activation of Glial fibrillary acidic protein + Retinal Glia. Using a dissociated Retinal ganglion cell culture model we showed that reducing the number of activated Retinal Glia with a Glial specific toxin, α-Aminoadipic acid, significantly reduced the growth potential of Retinal ganglion cells from glaucomatous rat eyes, suggesting that activated Retinal Glia mediate, at least in part, the growth promoting effect. This was shown to be mediated by both membrane-bound and soluble Glial-derived factors. Neurotrophin and ciliary neurotrophic/leukemia inhibitory factor blockers did not affect the regenerative potential, excluding these growth factors as principal mediators of the enhanced growth response occurring in glaucomatous Retinal cultures. These observations are the first to reveal that Retinal ganglion cells from glaucomatous rat eyes have an enhanced regenerative capacity. Furthermore, our results suggest that activated Retinal Glia mediate at least part of this response. Further work to understand and enhance the regeneration-promoting effect of activated Retinal Glia is required to determine if this approach could be useful as part of a therapeutic strategy to encourage optic nerve regeneration in glaucoma.
Takayuki Harada - One of the best experts on this subject based on the ideXlab platform.
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TrkB Signaling in Retinal Glia Stimulates Neuroprotection after Optic Nerve Injury.
The American Journal of Pathology, 2015Co-Authors: Chikako Harada, Yuriko Azuchi, Takahiko Noro, Xiaoli Guo, Atsuko Kimura, Kazuhiko Namekata, Takayuki HaradaAbstract:Brain-derived neurotrophic factor (BDNF) regulates neural cell survival mainly by activating TrkB receptors. Several lines of evidence support a key role for BDNF-TrkB signaling in survival of adult Retinal ganglion cells in animal models of optic nerve injury (ONI), but the neuroprotective effect of exogenous BDNF is transient. Glial cells have recently attracted considerable attention as mediators of neural cell survival, and TrkB expression in Retinal Glia suggests its role in neuroprotection. To elucidate this point directly, we examined the effect of ONI on TrkB flox/flox :Glial fibrillary acidic protein (GFAP)–Cre+ (TrkB GFAP ) knockout (KO) mice, in which TrkB is deleted in Retinal Glial cells. ONI markedly increased mRNA expression levels of basic fibroblast growth factor (bFGF) in wild-type (WT) mice but not in TrkB GFAP KO mice. Immunohistochemical analysis at 7 days after ONI (d7) revealed bFGF up-regulation mainly occurred in Muller Glia. ONI-induced Retinal ganglion cell loss in WT mice was consistently mild compared with TrkB GFAP KO mice at d7. On the other hand, ONI severely decreased TrkB expression in both WT and TrkB GFAP KO mice after d7, and the severity of Retinal degeneration was comparable with TrkB GFAP KO mice at d14. Our data provide direct evidence that Glial TrkB signaling plays an important role in the early stage of neural protection after traumatic injury.
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Glia and neuron specific functions of trkb signalling during Retinal degeneration and regeneration
Nature Communications, 2011Co-Authors: Chikako Harada, Xiaoli Guo, Atsuko Kimura, Kazuhiko Namekata, Kazuaki Nakamura, Kohichi Tanaka, Luis F Parada, Takayuki HaradaAbstract:Glia, the support cells of the central nervous system, have recently attracted considerable attention both as mediators of neural cell survival and as sources of neural regeneration. To further elucidate the role of Glial and neural cells in neurodegeneration, we generated TrkB(GFAP) and TrkB(c-kit) knockout mice in which TrkB, a receptor for brain-derived neurotrophic factor (BDNF), is deleted in Retinal Glia or inner Retinal neurons, respectively. Here, we show that the extent of glutamate-induced Retinal degeneration was similar in these two mutant mice. Furthermore in TrkB(GFAP) knockout mice, BDNF did not prevent photoreceptor degeneration and failed to stimulate Muller Glial cell proliferation and expression of neural markers in the degenerating retina. These results demonstrate that BDNF signalling in Glia has important roles in neural protection and regeneration, particularly in conversion of Muller Glia to photoreceptors. In addition, our genetic models provide a system in which Glia- and neuron-specific gene functions can be tested in central nervous system tissues in vivo.
Inge Van Hove - One of the best experts on this subject based on the ideXlab platform.
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Tightening the Retinal Glia limitans attenuates neuroinflammation after optic nerve injury.
Glia, 2020Co-Authors: Evy Lefevere, Manuel Salinas-navarro, Lien Andries, Lut Noterdaeme, Isabelle Etienne, Elien Van Wonterghem, Stefan Vinckier, Benjamin M. Davis, Tine Van Bergen, Inge Van HoveAbstract:Increasing evidence suggests that functional impairments at the level of the neurovascular unit (NVU) underlie many neurodegenerative and neuroinflammatory diseases. While being part of the NVU, astrocytes have been largely overlooked in this context and only recently, tightening of the Glia limitans has been put forward as an important neuroprotective response to limit these injurious processes. In this study, using the retina as a central nervous system (CNS) model organ, we investigated the structure and function of the Glia limitans, and reveal that the blood-retina barrier and Glia limitans function as a coordinated double barrier to limit infiltration of leukocytes and immune molecules. We provide in vitro and in vivo evidence for a protective response at the NVU upon CNS injury, which evokes inflammation-induced Glia limitans tightening. Matrix metalloproteinase-3 (MMP-3) was found to be a crucial regulator of this process, thereby revealing its beneficial and immunomodulatory role in the CNS. in vivo experiments in which MMP-3 activity was deleted via genetic and pharmacological approaches, combined with a comprehensive study of tight junction molecules, Glial end feet markers, myeloid cell infiltration, cytokine expression and neurodegeneration, show that MMP-3 attenuates neuroinflammation and neurodegeneration by tightening the Glia limitans, thereby pointing to a prominent role of MMP-3 in preserving the integrity of the NVU upon injury. Finally, we gathered promising evidence to suggest that IL1b, which is also regulated by MMP-3, is at least one of the molecular messengers that induces Glia limitans tightening in the injured CNS.
Ann Logan - One of the best experts on this subject based on the ideXlab platform.
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Activated Retinal Glia promote neurite outgrowth of Retinal ganglion cells via apolipoprotein E.
Journal of Neuroscience Research, 2009Co-Authors: Barbara Lorber, Martin Berry, Michael R. Douglas, Toru Nakazawa, Ann LoganAbstract:In the present study, we investigated the role and mechanism through which activated Retinal Glia stimulate Retinal ganglion cell (RGC) neurite outgrowth. We have found that the level of Retinal Glial activation correlates directly with enhanced RGC neurite outgrowth after a preconditioning intravitreal Zymosan injection. Reduction in the number of activated Glia in primary rat Retinal cultures led to significantly reduced RGC neurite outgrowth. Glial-related neurite outgrowth appears to be, at least in part, mediated via apolipoprotein E (ApoE), which is expressed by activated Retinal astrocytes and Muller Glia. ApoE-deficient mice showed significantly reduced RGC neurite outgrowth potential after intravitreal Zymosan injection compared with age-matched wild-type animals. These observations suggest that ApoE, expressed by activated Retinal Glia, stimulates RGC neurite outgrowth after intravitreal Zymosan injection.
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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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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.