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Mathias Bahr - One of the best experts on this subject based on the ideXlab platform.

  • morphological and functional analysis of an incomplete cns fiber tract Lesion graded crush of the rat Optic Nerve
    Journal of Neuroscience Methods, 2001
    Co-Authors: Nikolaj Klocker, Martin Zerfowski, Nils C Gellrich, Mathias Bahr
    Abstract:

    Fiber tract Lesions in the central nervous system (CNS) often induce delayed retrograde neuronal degeneration, a phenomenon that represents an important therapeutic challenge in clinical neurotraumatology. In the present study, we report an in vivo trauma model of graded axonal Lesion of CNS neurons. Controlled by a newtonmeter device, we induced retrograde degeneration of adult rat retinal ganglion cells (RGCs) by graded crush of the Optic Nerve. The extent of secondary RGC death increased linearly with the applied crush force. Moreover, visually evoked potentials were used to characterize the consequences of controlled Optic Nerve Lesion on the functional integrity of the visual projection. The presented model of fiber tract Lesion closely resembles the clinical conditions of traumatic brain injury and could prove useful to screen for neuroprotective drugs based on both a morphological and functional read-out.

  • graded expression patterns of ephrin as in the superior colliculus after Lesion of the adult mouse Optic Nerve
    Mechanisms of Development, 2001
    Co-Authors: Bernd Knoll, Stefan Isenmann, Mathias Bahr, Ertugrul Kilic, Jurgen Walkenhorst, Stefan Engel, Jens Wehinger, Uwe Drescher
    Abstract:

    The idea has been put forward that molecules and mechanisms acting during development are re-used during regeneration in the adult, for example in response to traumatic injury in order to re-establish the functional integrity of neuronal circuits. Members of the Eph family of receptor tyrosine kinases and their 'ligands', the ephrins, play a prominent role during development of the retinocollicular projection in rodents, where EphA receptors and ephrin-As are expressed in gradients in both the retina and the superior colliculi (SC). We were interested in investigating whether EphA family members are also expressed or re-expressed in the adult after Optic Nerve Lesion, since the presence of axon guidance information is an important prerequisite for a topographically appropriate re-connection by retinal ganglion cell (RGC) axons. This analysis was encouraged by results showing that RGC axons do not exert guidance preferences in response to membranes from adult unLesioned SC, but in response to membranes from the adult deafferented SC. We found a graded expression pattern of ephrin-As in the SC both before and after deafferentation, which was remarkably similar to those found during development. EphA receptor levels were reduced in the SC after deafferentation and the expression patterns of the EphB family were not changed. In particular, the presence of a graded ephrin-A expression in the deafferented SC suggests that - if robust regeneration of RGC axons can be achieved - topographic guidance information as a likely requirement for a functionally successful re-establishment of the retinocollicular projection is available.

  • expression of c jun protein in degenerating retinal ganglion cells after Optic Nerve Lesion in the rat
    Experimental Neurology, 1997
    Co-Authors: Stefan Isenmann, Mathias Bahr
    Abstract:

    Abstract Axonal Lesions to the Optic Nerve (ON) induce c-Jun expression in retinal ganglion cells (RGCs) of the ratin vivo.Detailed investigations using retrograde tracers, and double labeling studies for c-Jun and regeneration-associated factors, such as the growth-associated protein GAP-43, have suggested that this upregulation of c-Jun is part of a cell body response in an abortive attempt of affected RGCs to survive and regenerate an axon. On the other hand, prolonged expression of c-Jun protein has in several paradigms of neurodegeneration been linked to the induction of apoptotic cell death. In the present study, we examined the time course and subcellular localization of c-Jun protein by immunocytochemistry on retinal sections after Optic Nerve crush and carried out double labeling for c-Jun protein and DNA strand breaks to detect apoptosis on the same sections. Several days after ON Lesion, a subpopulation of RGCs was detected in which c-Jun protein was not confined to the nucleus, but also located in the cytoplasm. In addition, RGCs were seen that displayed morphological signs of apoptosis, DNA strand breaks, and c-Jun immunoreactivity at the same time. Therefore, c-Jun expression is not confined to intact or regenerating ganglion cells, but also occurs in cells that are destined to die. Our results suggest that the decision to undergo either fate depends on additional signaling events that modulate the transcriptional actions of c-Jun.

  • up regulation of bax protein in degenerating retinal ganglion cells precedes apoptotic cell death after Optic Nerve Lesion in the rat
    European Journal of Neuroscience, 1997
    Co-Authors: Stefan Isenmann, Claudia Wahl, Stanislaw Krajewski, John C Reed, Mathias Bahr
    Abstract:

    Retrograde degeneration of retinal ganglion cells as a consequence of Optic Nerve Lesion has been shown to fulfil the criteria of apoptosis. In the present study, we investigated the time course of ganglion cell apoptosis following intraorbital crushing of the Optic Nerve in adult rats using morphological criteria and applying a terminal transferase technique (TUNEL) for in situ detection of DNA strand breaks. In addition, we examined expression patterns of the anti-apoptotic proteins Bcl-2 and Bcl-X and the cell death-promoting protein Bax in retinae after crushing the Optic Nerve. Apoptotic nuclei were detected in the ganglion cell layer in the first 3 weeks after Optic Nerve crush, with a peak after 6 days. Bcl-2 and Bcl-X proteins were expressed in ganglion cells at low levels. Expression of Bcl-2 decreased further during the days following crush. Bcl-X expression was initially increased, followed by a decline over the following days. In contrast, Bax protein, which was expressed in most ganglion cells at moderate baseline levels, was sharply increased as early as 30 min after crush, reached peak levels after 3 days, and remained up-regulated for at least 1 week thereafter. Double labelling for Bax and TUNEL in retinal sections, however, did not reveal colocalization of the two signals in individual retinal ganglion cells, consistent with the idea that increases in Bax precede apoptosis after Optic Nerve Lesion. Thus, retinal ganglion cell death might be prevented by ablation of Bax protein in these cells, or by up-regulation of Bax-antagonists such as Bcl-2 or Bcl-X.

  • expression of jun krox and creb transcription factors in goldfish and rat retinal ganglion cells following Optic Nerve Lesion is related to axonal sprouting
    Journal of Neurobiology, 1993
    Co-Authors: Thomas Herdegen, Mathias Bahr, Claudia A O Stuermer, Martin Bastmeyer, R Bravo, M Zimmermann
    Abstract:

    Goldfish and rat Optic Nerves were cut and crushed, respectively, and the expression of the transcription factor proteins c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB was investigated in retinal ganglion cells (RGCs) by immunocytochemistry. Immunoreactivities (IRs) were followed up to 350 days in the goldfish and upto 22 days in the rat. In RGCs of untreated goldfish and rats, all JUN, FOS, and KROX proteins were absent whereas CREB was constitutively expressed. After Optic Nerve cut in goldfish, a JUN-like immunoreactivity (JUN-IR) appeared in a small number of RGCs of central retina after 24 h, reached a maximum within 5 days, declined after 30 days, and was on a half-maximal level after 50 days. Between 100 and 200 days, JUN-IR was only visible in a few RGCs and was completely absent after 350 days. Specific antibodies against c-JUN, JUN B, and JUN D gave no distinct immunoreactive signal. Thus, we could not determine which member of the JUN family contributed to the JUN-IR. The expression of CREB declined after 5 days. The number of CREB-labeled RGCs was reduced (not significant) and the intensity of labeling faded out. After 50 days, CREB-IR had returned to basal level. c-FOS, FOS B, and KROX-24 could not be detected in goldfish RGCs following Optic Nerve cut. After Optic Nerve crush in the rat, c-JUN, JUN D, and KROX-24 appeared in a substantial number of RGCs after 24 h, had a maximal expression after 5 days, and strongly declined after 8 days. c-JUN and KROX-24 were completely absent after 22 days whereas JUN D was still present in a few rat RGCs. The number of CREB-labeled RGCs decreased after 5 days and had declined by 50% after 22 days. Expression of JUN B, c-FOS, FOS B could not be detected in rat RGCs after Optic Nerve crush. Our data demonstrate that the decrease of CREB and the increase of JUN and KROX-24 transcription factors precedes and parallels both the alteration of de novo protein synthesis and the axonal sprouting, which are long lasting in goldfish and transient in rat. © 1993 John Wiley & Sons, Inc.

Stefan Isenmann - One of the best experts on this subject based on the ideXlab platform.

  • proliferative response of microglia and macrophages in the adult mouse eye after Optic Nerve Lesion
    Investigative Ophthalmology & Visual Science, 2010
    Co-Authors: Stefanie G Wohl, Christian Schmeer, Otto W Witte, Stefan Isenmann
    Abstract:

    PURPOSE: The purpose of this in vivo study was to evaluate the proliferative response of immunologic cells during the acute phase after Optic Nerve (ON) Lesion in the neural retina and the ciliary body (CB) in the adult mouse. METHODS: The number of cells obtained 5 to 10 days after ON crush was compared with that counted after intraorbital ON transection. In addition, after ON crush, the time course of in situ proliferating Ki67(+) microglia and macrophages was analyzed from 6 hours up to 10 days. RESULTS: The number of BrdU(+)F4/80(+) retinal microglia and ciliary macrophages increased over time, reaching the peak number 10 days after ON Lesion. In the retina, both ON Lesion types resulted in a similar number of BrdU(+)F4/80(+) microglia. Approximately 85% of all BrdU(+) cells were identified as F4/80(+) microglia. However, this cell population represented only 30% of all F4/80(+) microglia. The peak of microglial in situ proliferation was found 2 days after ON crush. In the CB, both ON Lesion types induced a significant increase in the number of BrdU(+)F4/80(+) macrophages. Of interest, the number of cells after ON transection further increased over time, whereas those after ON crush did not. CONCLUSIONS: ON Lesion significantly increased proliferation of F4/80(+) immunologic cells in both the retina and CB. Although no significant differences in cellular response were observed in the retina between both Lesion types, ON transection had a more pronounced effect on ciliary macrophages than did ON crush. Therefore, both regions seem not to act in concert during the acute phase after ON Lesion.

  • Optic Nerve Lesion increases cell proliferation and nestin expression in the adult mouse eye in vivo
    Experimental Neurology, 2009
    Co-Authors: Stefanie G Wohl, Christian Schmeer, Otto W Witte, Alexandra Kretz, Stefan Isenmann
    Abstract:

    In the naive adult rodent eye cell proliferation does not occur. The aim of this in vivo study was to evaluate if quiescent putative progenitor-like cells within the adult mouse eye can be activated by Optic Nerve (ON) injury. For a comprehensive analysis, three areas were assessed: the ON, the neural retina, and the ciliary body (CB). Two Lesion types were performed, i.e. intraorbital ON transection, or ON crush Lesion, in order to analyse possible differences in cellular response after injury. This mouse study shows, for the first time that ON Lesion up-regulates cell proliferation and nestin expression in the mouse eye as compared to naive controls. Numbers and distribution patterns of BrdU+ cells obtained were similar after both Lesion types, suggesting analogous mechanisms of activation. Interestingly, a differential cell proliferative response was observed in the CB. After ON Lesion, the absence of BrdU/TUNEL co-labelled cells confirmed that BrdU+ cells were indeed proliferating. Following ON Lesion, in the retina approximately 18% of all BrdU+ cells were positive for the neural stem cell/progenitor cell (NSC/PC) marker nestin. The fraction of BrdU+/nestin+ cells in the CB was approximately 26%. Most of the BrdU+/nestin+ cells found in the neural retina were identified as reactive astrocytes and Muller cells. Since reactive glia cells can participate in adult neuro- and gliogenesis this may indicate a potential for regeneration after ON Lesion in vivo.

  • graded expression patterns of ephrin as in the superior colliculus after Lesion of the adult mouse Optic Nerve
    Mechanisms of Development, 2001
    Co-Authors: Bernd Knoll, Stefan Isenmann, Mathias Bahr, Ertugrul Kilic, Jurgen Walkenhorst, Stefan Engel, Jens Wehinger, Uwe Drescher
    Abstract:

    The idea has been put forward that molecules and mechanisms acting during development are re-used during regeneration in the adult, for example in response to traumatic injury in order to re-establish the functional integrity of neuronal circuits. Members of the Eph family of receptor tyrosine kinases and their 'ligands', the ephrins, play a prominent role during development of the retinocollicular projection in rodents, where EphA receptors and ephrin-As are expressed in gradients in both the retina and the superior colliculi (SC). We were interested in investigating whether EphA family members are also expressed or re-expressed in the adult after Optic Nerve Lesion, since the presence of axon guidance information is an important prerequisite for a topographically appropriate re-connection by retinal ganglion cell (RGC) axons. This analysis was encouraged by results showing that RGC axons do not exert guidance preferences in response to membranes from adult unLesioned SC, but in response to membranes from the adult deafferented SC. We found a graded expression pattern of ephrin-As in the SC both before and after deafferentation, which was remarkably similar to those found during development. EphA receptor levels were reduced in the SC after deafferentation and the expression patterns of the EphB family were not changed. In particular, the presence of a graded ephrin-A expression in the deafferented SC suggests that - if robust regeneration of RGC axons can be achieved - topographic guidance information as a likely requirement for a functionally successful re-establishment of the retinocollicular projection is available.

  • expression of c jun protein in degenerating retinal ganglion cells after Optic Nerve Lesion in the rat
    Experimental Neurology, 1997
    Co-Authors: Stefan Isenmann, Mathias Bahr
    Abstract:

    Abstract Axonal Lesions to the Optic Nerve (ON) induce c-Jun expression in retinal ganglion cells (RGCs) of the ratin vivo.Detailed investigations using retrograde tracers, and double labeling studies for c-Jun and regeneration-associated factors, such as the growth-associated protein GAP-43, have suggested that this upregulation of c-Jun is part of a cell body response in an abortive attempt of affected RGCs to survive and regenerate an axon. On the other hand, prolonged expression of c-Jun protein has in several paradigms of neurodegeneration been linked to the induction of apoptotic cell death. In the present study, we examined the time course and subcellular localization of c-Jun protein by immunocytochemistry on retinal sections after Optic Nerve crush and carried out double labeling for c-Jun protein and DNA strand breaks to detect apoptosis on the same sections. Several days after ON Lesion, a subpopulation of RGCs was detected in which c-Jun protein was not confined to the nucleus, but also located in the cytoplasm. In addition, RGCs were seen that displayed morphological signs of apoptosis, DNA strand breaks, and c-Jun immunoreactivity at the same time. Therefore, c-Jun expression is not confined to intact or regenerating ganglion cells, but also occurs in cells that are destined to die. Our results suggest that the decision to undergo either fate depends on additional signaling events that modulate the transcriptional actions of c-Jun.

  • up regulation of bax protein in degenerating retinal ganglion cells precedes apoptotic cell death after Optic Nerve Lesion in the rat
    European Journal of Neuroscience, 1997
    Co-Authors: Stefan Isenmann, Claudia Wahl, Stanislaw Krajewski, John C Reed, Mathias Bahr
    Abstract:

    Retrograde degeneration of retinal ganglion cells as a consequence of Optic Nerve Lesion has been shown to fulfil the criteria of apoptosis. In the present study, we investigated the time course of ganglion cell apoptosis following intraorbital crushing of the Optic Nerve in adult rats using morphological criteria and applying a terminal transferase technique (TUNEL) for in situ detection of DNA strand breaks. In addition, we examined expression patterns of the anti-apoptotic proteins Bcl-2 and Bcl-X and the cell death-promoting protein Bax in retinae after crushing the Optic Nerve. Apoptotic nuclei were detected in the ganglion cell layer in the first 3 weeks after Optic Nerve crush, with a peak after 6 days. Bcl-2 and Bcl-X proteins were expressed in ganglion cells at low levels. Expression of Bcl-2 decreased further during the days following crush. Bcl-X expression was initially increased, followed by a decline over the following days. In contrast, Bax protein, which was expressed in most ganglion cells at moderate baseline levels, was sharply increased as early as 30 min after crush, reached peak levels after 3 days, and remained up-regulated for at least 1 week thereafter. Double labelling for Bax and TUNEL in retinal sections, however, did not reveal colocalization of the two signals in individual retinal ganglion cells, consistent with the idea that increases in Bax precede apoptosis after Optic Nerve Lesion. Thus, retinal ganglion cell death might be prevented by ablation of Bax protein in these cells, or by up-regulation of Bax-antagonists such as Bcl-2 or Bcl-X.

Jost B Jonas - One of the best experts on this subject based on the ideXlab platform.

  • effect of brimonidine on retinal ganglion cell survival in an Optic Nerve crush model
    American Journal of Ophthalmology, 2009
    Co-Authors: Liang Xu, Haijuan Zhang, Shixian Zhang, Mingliang Pu, Jost B Jonas
    Abstract:

    Purpose To investigate the effect of brimonidine on the retinal ganglion cell survival in an Optic Nerve crush model. Design Experimental animal study. Methods Twenty-four Sprague-Dawley rats were divided into a study group of eight animals receiving intraperitoneal injections of brimonidine (1 mg/kg) and into a control group of 12 animals receiving intraperitoneal saline injections. All injections were performed one hour before the Optic Nerve crash and daily afterwards. For each animal, the right Optic Nerve was crushed for 60 seconds by a microclip with 40-g power. At 23 days after the Optic Nerve crush, the retinal ganglion cells were retrogradely labeled by injecting 3% fluorogold into both sides of the superior colliculus of the brain. At four weeks after the Optic Nerve crush, the animals were sacrificed. Photographs taken from retinal flat mounts were assessed for number and density of the retinal ganglion cells. Results The retinal ganglion cell density of the right eyes with an Optic Nerve Lesion was statistically significantly ( P = .02) higher in the brimonidine study group (1281 ± 189 cells/mm 2 ) than in the control group (1060 ± 148 cells/mm 2 ). Correspondingly, the survival rate (ratio of retinal ganglion cell density in the right eye divided by cell density in the left eye) was statistically significantly ( P = .027) higher in the study group than in the control group (61.0% ± 6.0% vs 53.5±8.0%). Conclusion Intraperitoneal injections of brimonidine given prophylactically prior to and posttreatment daily after an experimental and standardized Optic Nerve crush in rats were associated with a higher survival rate of retinal ganglion cells.

  • effect of brimonidine on retinal ganglion cell survival in an Optic Nerve crush model
    American Journal of Ophthalmology, 2009
    Co-Authors: Haijuan Zhang, Shixian Zhang, Jost B Jonas
    Abstract:

    Purpose To investigate the effect of brimonidine on the retinal ganglion cell survival in an Optic Nerve crush model. Design Experimental animal study. Methods Twenty-four Sprague-Dawley rats were divided into a study group of eight animals receiving intraperitoneal injections of brimonidine (1 mg/kg) and into a control group of 12 animals receiving intraperitoneal saline injections. All injections were performed one hour before the Optic Nerve crash and daily afterwards. For each animal, the right Optic Nerve was crushed for 60 seconds by a microclip with 40-g power. At 23 days after the Optic Nerve crush, the retinal ganglion cells were retrogradely labeled by injecting 3% fluorogold into both sides of the superior colliculus of the brain. At four weeks after the Optic Nerve crush, the animals were sacrificed. Photographs taken from retinal flat mounts were assessed for number and density of the retinal ganglion cells. Results The retinal ganglion cell density of the right eyes with an Optic Nerve Lesion was statistically significantly ( P = .02) higher in the brimonidine study group (1281 ± 189 cells/mm 2 ) than in the control group (1060 ± 148 cells/mm 2 ). Correspondingly, the survival rate (ratio of retinal ganglion cell density in the right eye divided by cell density in the left eye) was statistically significantly ( P = .027) higher in the study group than in the control group (61.0% ± 6.0% vs 53.5±8.0%). Conclusion Intraperitoneal injections of brimonidine given prophylactically prior to and posttreatment daily after an experimental and standardized Optic Nerve crush in rats were associated with a higher survival rate of retinal ganglion cells.

Barbara Lorber - One of the best experts on this subject based on the ideXlab platform.

  • retinal ganglion cell survival and axon regeneration in wlds transgenic rats after Optic Nerve crush and lens injury
    BMC Neuroscience, 2012
    Co-Authors: Barbara Lorber, Alessia Tassoni, Natalie D Bull, Marilita M Moschos, Keith R. Martin
    Abstract:

    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.

  • Different factors promote axonal regeneration of adult rat retinal ganglion cells after lens injury and intravitreal peripheral Nerve grafting
    Journal of Neuroscience Research, 2008
    Co-Authors: Barbara Lorber, Martin Berry, Ann Logan
    Abstract:

    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.

  • lens injury stimulates adult mouse retinal ganglion cell axon regeneration via both macrophage and lens derived factors
    European Journal of Neuroscience, 2005
    Co-Authors: Barbara Lorber, Martin Berry, Ann Logan
    Abstract:

    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.

Ann Logan - One of the best experts on this subject based on the ideXlab platform.

  • Different factors promote axonal regeneration of adult rat retinal ganglion cells after lens injury and intravitreal peripheral Nerve grafting
    Journal of Neuroscience Research, 2008
    Co-Authors: Barbara Lorber, Martin Berry, Ann Logan
    Abstract:

    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.

  • lens injury stimulates adult mouse retinal ganglion cell axon regeneration via both macrophage and lens derived factors
    European Journal of Neuroscience, 2005
    Co-Authors: Barbara Lorber, Martin Berry, Ann Logan
    Abstract:

    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.