scholarly journals Nav1.6 promotes inflammation and neuronal degeneration in a mouse model of multiple sclerosis

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Barakat Alrashdi ◽  
Bassel Dawod ◽  
Andrea Schampel ◽  
Sabine Tacke ◽  
Stefanie Kuerten ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Retinal Ganglion Cells ◽  
Axonal Degeneration ◽  
Ganglion Cells ◽  
Neuronal Degeneration ◽  
Retinal Ganglion ◽  
Autoimmune Encephalomyelitis ◽  
Aav Vector ◽  
Α Subunit

Abstract Background In multiple sclerosis (MS) and in the experimental autoimmune encephalomyelitis (EAE) model of MS, the Nav1.6 voltage-gated sodium (Nav) channel isoform has been implicated as a primary contributor to axonal degeneration. Following demyelination Nav1.6, which is normally co-localized with the Na+/Ca2+ exchanger (NCX) at the nodes of Ranvier, associates with β-APP, a marker of neural injury. The persistent influx of sodium through Nav1.6 is believed to reverse the function of NCX, resulting in an increased influx of damaging Ca2+ ions. However, direct evidence for the role of Nav1.6 in axonal degeneration is lacking. Methods In mice floxed for Scn8a, the gene that encodes the α subunit of Nav1.6, subjected to EAE we examined the effect of eliminating Nav1.6 from retinal ganglion cells (RGC) in one eye using an AAV vector harboring Cre and GFP, while using the contralateral either injected with AAV vector harboring GFP alone or non-targeted eye as control. Results In retinas, the expression of Rbpms, a marker for retinal ganglion cells, was found to be inversely correlated to the expression of Scn8a. Furthermore, the gene expression of the pro-inflammatory cytokines Il6 (IL-6) and Ifng (IFN-γ), and of the reactive gliosis marker Gfap (GFAP) were found to be reduced in targeted retinas. Optic nerves from targeted eyes were shown to have reduced macrophage infiltration and improved axonal health. Conclusion Taken together, our results are consistent with Nav1.6 promoting inflammation and contributing to axonal degeneration following demyelination.

scholarly journals Matrine protects retinal ganglion cells from apoptosis in experimental optic neuritis

2019 ◽  
Author(s):  
Jian Kang ◽  
Shu-Qing Liu ◽  
Yi-Fan Song ◽  
Meng-Ru Wang ◽  
Yao-Juan Chu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Neuronal Damage ◽  
Disease Onset ◽  
High Dose ◽  
Retinal Ganglion ◽  
Autoimmune Encephalomyelitis

Abstract Background: Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of blindness in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on ON in rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Results: MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1+ macrophages/microglia and CD4+ T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, and decreased apoptosis in retinal ganglion cells (RGCs) were also observed after MAT treatment. Conclusions: Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that causes blindness.

scholarly journals Matrine protects retinal ganglion cells from apoptosis in experimental optic neuritis

2020 ◽  
Author(s):  
Jian Kang ◽  
Shu-Qing Liu ◽  
Yi-Fan Song ◽  
Meng-Ru Wang ◽  
Yao-Juan Chu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Neuronal Damage ◽  
Disease Onset ◽  
High Dose ◽  
Retinal Ganglion ◽  
Autoimmune Encephalomyelitis

Abstract Background: Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of blindness in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on ON in rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Results: MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1+ macrophages/microglia and CD4+ T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, and decreased apoptosis in retinal ganglion cells (RGCs) were also observed after MAT treatment. Conclusions: Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that causes blindness.

scholarly journals The Role of N-Methyl-D-Aspartate Receptor Activation in Homocysteine-Induced Death of Retinal Ganglion Cells

2011 ◽  
Vol 52 (8) ◽  
pp. 5515 ◽  
Author(s):  
Preethi S. Ganapathy ◽  
Richard E. White ◽  
Yonju Ha ◽  
B. Renee Bozard ◽  
Paul L. McNeil ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Receptor Activation ◽  
Retinal Ganglion ◽  
Aspartate Receptor

scholarly journals Hyperhomocysteinemia-induced death of retinal ganglion cells: The role of Müller glial cells and NRF2

Redox Biology ◽  
2019 ◽  
Vol 24 ◽  
pp. 101199 ◽  
Author(s):  
Soumya Navneet ◽  
Jing Zhao ◽  
Jing Wang ◽  
Barbara Mysona ◽  
Shannon Barwick ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Glial Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Müller Glial Cells

Loss of Retinal Ganglion Cells Following Retinal Ischemia: The Role of Inducible Nitric Oxide Synthase

2002 ◽  
Vol 75 (5) ◽  
pp. 521-528 ◽  
Author(s):  
Arthur H. Neufeld ◽  
Shin-ichiro Kawai ◽  
Sucharita Das ◽  
Smita Vora ◽  
Elizabeth Gachie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Retinal Ganglion Cells ◽  
Inducible Nitric Oxide Synthase ◽  
Ganglion Cells ◽  
Retinal Ischemia ◽  
Retinal Ganglion ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Neuroactive peptides as markers of retinal ganglion cell populations that differ in anatomical organization and function

1988 ◽  
Vol 1 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Rodrigo O. Kuljis ◽  
Harvey J. Karten
Keyword(s):  
Retinal Ganglion Cells ◽  
Optic Tectum ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Pharmacological Manipulation ◽  
Functional Aspects ◽  
Neuroactive Peptides ◽  
Retinofugal Projections ◽  
And Function

AbstractRecent immunocytochemical studies indicate the existence of several classes of peptide- (PRGC) and catecholamine-containing retinal ganglion cells in anurans, birds, and mammals. Different classes of PRGC project to discrete and seemingly unique layers in the retino-recipient portion of the anuran and avian optic tectum. Peptide-containing retinofugal projections to the frog tectum originate early in development, and are reestablished by some classes of PRGC during regeneration of the optic nerve. These findings indicate that chemically specific, parallel retinofugal pathways presumably subserve different functional aspects of vision in vertebrates. Exciting prospects for research include the correlation of physiologically with immunocytochemically defined classes of retinal ganglion cells, the analysis of the possible role of neuroactive peptides in retinofugal transmission, and the pharmacological manipulation of putative peptidergic retinofugal pathways to analyze their role in visual function.

Sign in / Sign up

Export Citation Format

Share Document