Optic nerve and vitreal inflammation are both RGC neuroprotective but only the latter is RGC axogenic

Intravitreal inflammation, induced by either lens injury, or intravitreal injection of zymosan (IVZ), protects RGC from apoptosis and stimulates axon regeneration after optic nerve transection. Here, we investigate the differential effects of intra-optic nerve zymosan (ONZ) and IVZ injections on RGC...

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Main Authors: Zubair Ahmed, Mudasser Aslam, Barbara Lorber, Ellen L. Suggate, Martin Berry, Ann Logan
Format: Article
Language:English
Published: Elsevier 2010-02-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996109003106
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author Zubair Ahmed
Mudasser Aslam
Barbara Lorber
Ellen L. Suggate
Martin Berry
Ann Logan
author_facet Zubair Ahmed
Mudasser Aslam
Barbara Lorber
Ellen L. Suggate
Martin Berry
Ann Logan
author_sort Zubair Ahmed
collection DOAJ
description Intravitreal inflammation, induced by either lens injury, or intravitreal injection of zymosan (IVZ), protects RGC from apoptosis and stimulates axon regeneration after optic nerve transection. Here, we investigate the differential effects of intra-optic nerve zymosan (ONZ) and IVZ injections on RGC neuroprotection and axogenesis. After both IVZ and ONZ injection, zymosan-induced inflammation promoted a similar 4-/5-fold enhancement in RGC survival, compared to optic nerve transected controls, but only IVZ promoted RGC axon regeneration. IVZ was the most effective in activating retinal astrocyte/Müller cells while regulated intramembraneous proteolysis (RIP) of p75NTR and inactivation of Rho (key components of the axon growth inhibitory signalling cascade) occurred in both ONZ and IVZ, but only in the latter did RGC axons regenerate. We suggest that neuroprotective factors may be transported to RGC somata by retrograde transport after ONZ and diffuse into the retina after IVZ injection, but an axogenic agent is required to initiate and maintain disinhibited RGC axon regeneration that may be an exclusive property of a Müller cell-derived factor released after IVZ.
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spelling doaj.art-efeb04b7147e4a8dbe670ef303bf80282022-12-21T23:24:30ZengElsevierNeurobiology of Disease1095-953X2010-02-01372441454Optic nerve and vitreal inflammation are both RGC neuroprotective but only the latter is RGC axogenicZubair Ahmed0Mudasser Aslam1Barbara Lorber2Ellen L. Suggate3Martin Berry4Ann Logan5Corresponding author. Fax: +44 121 414 8867.; Molecular Neuroscience Group, Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UKMolecular Neuroscience Group, Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UKMolecular Neuroscience Group, Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UKMolecular Neuroscience Group, Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UKMolecular Neuroscience Group, Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UKMolecular Neuroscience Group, Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UKIntravitreal inflammation, induced by either lens injury, or intravitreal injection of zymosan (IVZ), protects RGC from apoptosis and stimulates axon regeneration after optic nerve transection. Here, we investigate the differential effects of intra-optic nerve zymosan (ONZ) and IVZ injections on RGC neuroprotection and axogenesis. After both IVZ and ONZ injection, zymosan-induced inflammation promoted a similar 4-/5-fold enhancement in RGC survival, compared to optic nerve transected controls, but only IVZ promoted RGC axon regeneration. IVZ was the most effective in activating retinal astrocyte/Müller cells while regulated intramembraneous proteolysis (RIP) of p75NTR and inactivation of Rho (key components of the axon growth inhibitory signalling cascade) occurred in both ONZ and IVZ, but only in the latter did RGC axons regenerate. We suggest that neuroprotective factors may be transported to RGC somata by retrograde transport after ONZ and diffuse into the retina after IVZ injection, but an axogenic agent is required to initiate and maintain disinhibited RGC axon regeneration that may be an exclusive property of a Müller cell-derived factor released after IVZ.http://www.sciencedirect.com/science/article/pii/S0969996109003106MacrophagesRGC survival/axon regenerationMüller cellsAstrocytesNeurite outgrowthZymosan
spellingShingle Zubair Ahmed
Mudasser Aslam
Barbara Lorber
Ellen L. Suggate
Martin Berry
Ann Logan
Optic nerve and vitreal inflammation are both RGC neuroprotective but only the latter is RGC axogenic
Neurobiology of Disease
Macrophages
RGC survival/axon regeneration
Müller cells
Astrocytes
Neurite outgrowth
Zymosan
title Optic nerve and vitreal inflammation are both RGC neuroprotective but only the latter is RGC axogenic
title_full Optic nerve and vitreal inflammation are both RGC neuroprotective but only the latter is RGC axogenic
title_fullStr Optic nerve and vitreal inflammation are both RGC neuroprotective but only the latter is RGC axogenic
title_full_unstemmed Optic nerve and vitreal inflammation are both RGC neuroprotective but only the latter is RGC axogenic
title_short Optic nerve and vitreal inflammation are both RGC neuroprotective but only the latter is RGC axogenic
title_sort optic nerve and vitreal inflammation are both rgc neuroprotective but only the latter is rgc axogenic
topic Macrophages
RGC survival/axon regeneration
Müller cells
Astrocytes
Neurite outgrowth
Zymosan
url http://www.sciencedirect.com/science/article/pii/S0969996109003106
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AT ellenlsuggate opticnerveandvitrealinflammationarebothrgcneuroprotectivebutonlythelatterisrgcaxogenic
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