Deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis.

Vision impairment due to optic neuritis (ON) is one of the major clinical presentations in Multiple Sclerosis (MS) and is characterized by inflammation and degeneration of the optic nerve and retina. Currently available treatments are only partially effective and have a limited impact on the neuroin...

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Main Authors: Amritha A Candadai, Fang Liu, Abdelrahman Y Fouda, Moaddey Alfarhan, Chithra D Palani, Zhimin Xu, Ruth B Caldwell, S Priya Narayanan
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0247901&type=printable
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author Amritha A Candadai
Fang Liu
Abdelrahman Y Fouda
Moaddey Alfarhan
Chithra D Palani
Zhimin Xu
Ruth B Caldwell
S Priya Narayanan
author_facet Amritha A Candadai
Fang Liu
Abdelrahman Y Fouda
Moaddey Alfarhan
Chithra D Palani
Zhimin Xu
Ruth B Caldwell
S Priya Narayanan
author_sort Amritha A Candadai
collection DOAJ
description Vision impairment due to optic neuritis (ON) is one of the major clinical presentations in Multiple Sclerosis (MS) and is characterized by inflammation and degeneration of the optic nerve and retina. Currently available treatments are only partially effective and have a limited impact on the neuroinflammatory pathology of the disease. A recent study from our laboratory highlighted the beneficial effect of arginase 2 (A2) deletion in suppressing retinal neurodegeneration and inflammation in an experimental model of MS. Utilizing the same model, the present study investigated the impact of A2 deficiency on MS-induced optic neuritis. Experimental autoimmune encephalomyelitis (EAE) was induced in wild-type (WT) and A2 knockout (A2-/-) mice. EAE-induced cellular infiltration, as well as activation of microglia and macrophages, were reduced in A2-/- optic nerves. Axonal degeneration and demyelination seen in EAE optic nerves were observed to be reduced with A2 deletion. Further, the lack of A2 significantly ameliorated astrogliosis induced by EAE. In conclusion, our findings demonstrate a critical involvement of arginase 2 in mediating neuroinflammation in optic neuritis and suggest the potential of A2 blockade as a targeted therapy for MS-induced optic neuritis.
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spelling doaj-art-274aeb5ae28b4b918a2679c336cb5cd52025-08-20T02:00:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01163e024790110.1371/journal.pone.0247901Deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis.Amritha A CandadaiFang LiuAbdelrahman Y FoudaMoaddey AlfarhanChithra D PalaniZhimin XuRuth B CaldwellS Priya NarayananVision impairment due to optic neuritis (ON) is one of the major clinical presentations in Multiple Sclerosis (MS) and is characterized by inflammation and degeneration of the optic nerve and retina. Currently available treatments are only partially effective and have a limited impact on the neuroinflammatory pathology of the disease. A recent study from our laboratory highlighted the beneficial effect of arginase 2 (A2) deletion in suppressing retinal neurodegeneration and inflammation in an experimental model of MS. Utilizing the same model, the present study investigated the impact of A2 deficiency on MS-induced optic neuritis. Experimental autoimmune encephalomyelitis (EAE) was induced in wild-type (WT) and A2 knockout (A2-/-) mice. EAE-induced cellular infiltration, as well as activation of microglia and macrophages, were reduced in A2-/- optic nerves. Axonal degeneration and demyelination seen in EAE optic nerves were observed to be reduced with A2 deletion. Further, the lack of A2 significantly ameliorated astrogliosis induced by EAE. In conclusion, our findings demonstrate a critical involvement of arginase 2 in mediating neuroinflammation in optic neuritis and suggest the potential of A2 blockade as a targeted therapy for MS-induced optic neuritis.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0247901&type=printable
spellingShingle Amritha A Candadai
Fang Liu
Abdelrahman Y Fouda
Moaddey Alfarhan
Chithra D Palani
Zhimin Xu
Ruth B Caldwell
S Priya Narayanan
Deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis.
PLoS ONE
title Deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis.
title_full Deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis.
title_fullStr Deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis.
title_full_unstemmed Deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis.
title_short Deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis.
title_sort deletion of arginase 2 attenuates neuroinflammation in an experimental model of optic neuritis
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0247901&type=printable
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