Matrine treatment reduces retinal ganglion cell apoptosis in experimental optic neuritis

Jian Kang,Lin Zhu,Yaojuan Chu,Yamin Shi,Mengru Wang,Fengyan Zhang,Yifan Song,Shuqing Liu

doi:10.1038/s41598-021-89086-7

Abstract

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 visual disturbance 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 rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. 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, reduced numbers of apoptosis in retinal ganglion cells (RGCs). Moreover, MAT treatment promoted Akt phosphorylation and shifted the Bcl-2/Bax ratio back towards an antiapoptotic one, which could be a mechanism for its therapeutic effect in the ON model. 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 may result in blindness.

Highlights

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 visual disturbance in young adults
A similar pattern was observed in CD4+ T cells, for which a significant reduction was observed after MAT treatment compared with vehicle treatment (Fig. 3D–F)
When optic nerve and retina sections of all rats were stained with the NF antibody (Fig. 5A), our results showed that NF expression was significantly decreased in optic nerves of immunized rats compared with naïve ones, while this expression was markedly increased after MAT treatment (Fig. 5B, C)

Summary

Introduction

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 visual disturbance in young adults. Our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. In the animal model of relapsing/ remitting EAE, RGC apoptosis begins within a few days after onset of optic nerve inflammation[12,13], suggesting that axonal damage and cell loss are induced by optic nerve inflammation. By using experimental ON in an EAE rat model, we examined the effect of MAT on inflammatory cell infiltration, demyelination, and neurodegeneration and RGCs apoptosis of the optic nerve, and the molecular mechanism underlying its therapeutic benefits has been addressed

Methods

Results

Conclusion