Logo image
Back
Transgenic inhibition of astroglial NF-kappa B protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis
Journal article   Open access   Peer reviewed

Transgenic inhibition of astroglial NF-kappa B protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis

Roberta Brambilla, Galina Dvoriantchikova, David Barakat, Dmitry Ivanov, John R. Bethea and Valery I. Shestopalov
Journal of neuroinflammation, v 9(1), pp 213-213
10 Sep 2012
DOI: https://doi.org/10.1186/1742-2094-9-213
PMID: 22963651
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1186/1742-2094-9-213View
Published, Version of Record (VoR) Open

Abstract

Immunology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Science & Technology
Background: Optic neuritis is an acute, demyelinating neuropathy of the optic nerve often representing the first appreciable symptom of multiple sclerosis. Wallerian degeneration of irreversibly damaged optic nerve axons leads to death of retinal ganglion cells, which is the cause of permanent visual impairment. Although the specific mechanisms responsible for triggering these events are unknown, it has been suggested that a key pathological factor is the activation of immune-inflammatory processes secondary to leukocyte infiltration. However, to date, there is no conclusive evidence to support such a causal role for infiltrating peripheral immune cells in the etiopathology of optic neuritis. Methods: To dissect the contribution of the peripheral immune-inflammatory response versus the CNS-specific inflammatory response in the development of optic neuritis, we analyzed optic nerve and retinal ganglion cells pathology in wild-type and GFAP-I kappa Ba-dn transgenic mice, where NF-kappa B is selectively inactivated in astrocytes, following induction of EAE. Results: We found that, in wild-type mice, axonal demyelination in the optic nerve occurred as early as 8 days post induction of EAE, prior to the earliest signs of leukocyte infiltration (20 days post induction). On the contrary, GFAP-I kappa Ba-dn mice were significantly protected and showed a nearly complete prevention of axonal demyelination, as well as a drastic attenuation in retinal ganglion cell death. This correlated with a decrease in the expression of pro-inflammatory cytokines, chemokines, adhesion molecules, as well as a prevention of NAD(P) H oxidase subunit upregulation. Conclusions: Our results provide evidence that astrocytes, not infiltrating immune cells, play a key role in the development of optic neuritis and that astrocyte-mediated neurotoxicity is dependent on activation of a transcriptional program regulated by NF-kappa B. Hence, interventions targeting the NF-kappa B transcription factor in astroglia may be of therapeutic value in the treatment of optic neuritis associated with multiple sclerosis.

Metrics

9 Record Views
84 citations in Web of Science
91 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
Neurosciences
Logo image