Neuroprotective Effects of Fingolimod Supplement on the Retina and Optic Nerve in the Mouse Model of Experimental Autoimmune Encephalomyelitis.
Neuroprotective Effects of Fingolimod Supplement on the Retina and Optic Nerve in the Mouse Model of Experimental Autoimmune Encephalomyelitis.
复制标题
DOI：
10.3389/fnins.2021.663541
复制
发表时间：
2021
影响因子：
4.3
通讯作者：
Fan Y
中科院分区：
文献类型：
--
作者：
Yang T;Zha Z;Yang X;Kang Y;Wang X;Tong Y;Zhao X;Wang L;Fan Y
已经报道了在多发性硬化（MS）患者中长期施用芬戈莫德疗法所产生的有利效果，但是也记录了偶发的副作用，例如可逆性黄斑水肿。本研究旨在确定芬戈莫德治疗是否有益于实验性自身免疫性脑脊髓炎（EAE）小鼠的视觉系统。在芬戈莫德治疗的EAE中观察到视神经中的脱髓鞘和轴突损失以及细胞浸润，特别是募集的巨噬细胞减少。Fingolimod给药减少了EAE中视网膜和视神经中大胶质细胞的过度胶质增生，包括星形胶质细胞和Müller细胞。与对照组相比，EAE小鼠的视网膜和视神经中的小胶质细胞过度活化，这可以通过芬戈莫德治疗来缓解。此外，与未治疗的EAE小鼠相比，芬戈莫德治疗显著减少了视神经中视网膜神经节细胞（RGC）和少突胶质细胞的凋亡。这些结果表明，芬戈莫德对EAE小鼠模型的视网膜和视神经具有神经保护和抗炎作用。考虑到芬戈莫德对视觉系统有利和副作用的矛盾，我们推测MS治疗期间芬戈莫德引起的副作用（包括黄斑水肿）倾向于血管源性，而不是视神经和视网膜的胶质增生，这需要进一步的神经眼科研究。我们的研究结果表明，芬戈莫德是一种潜在的治疗方法，以防止EAE引起的视觉障碍。此外，我们表明，观察到的芬戈莫德的神经眼科保护作用依赖于阻碍视网膜和视神经中的胶质增生。
Favorable effects exerted by long-term administration of fingolimod therapy in multiple sclerosis (MS) patients have been reported, but sporadic side effects, such as reversible macular edema, also have been recorded. The present study aimed to determine whether fingolimod therapy is beneficial to the visual system in experimental autoimmune encephalomyelitis (EAE) mice. A decrease in demyelination and axon loss in the optic nerve as well as cellular infiltration, especially the recruited macrophages, was observed in EAE with fingolimod treatment. Fingolimod administration diminished hypergliosis of macroglia, including astrocytes and Müller cells in the retina and optic nerve in EAE. Microglia were hyperactivated in the retina and optic nerve in the EAE mice compared to controls, which could be alleviated by fingolimod treatment. Moreover, apoptosis of retinal ganglion cells (RGC) and oligodendrocytes in the optic nerve was significantly reduced with fingolimod treatment compared to that in the untreated EAE mice. These results suggested that fingolimod exerts neuroprotective and anti-inflammatory effects on the retina and optic nerve in a mouse model of EAE. Considering the paradox of favorable and side effects of fingolimod on visual system, we speculate that side effects including macular oedema caused by fingolimod during MS treatment is tendency to be vasogenic rather than hypergliosis in optic nerve and retina which warrants further neuroophthalmological investigation. Our results show that fingolimod is a potential therapeutic approach to prevent EAE-induced visual impairment. Moreover, we show that the observed neuro-ophthalmological protective effects of fingolimod were dependent on hampering hyper-gliosis in the retina and optic nerve.
登录
查看更多内容
影响因子：
9.3
作者：
Ambrosius B;Pitarokoili K;Schrewe L;Pedreiturria X;Motte J;Gold R
通讯作者：
Gold R
影响因子：
7.5
作者：
Bravo B;Gallego MI;Flores AI;Bornstein R;Puente-Bedia A;Hernández J;de la Torre P;García-Zaragoza E;Perez-Tavarez R;Grande J;Ballester A;Ballester S
通讯作者：
Ballester S
影响因子：
3.9
作者：
Mandal, P.;Gupta, A.;Yang, Y.
通讯作者：
Yang, Y.
影响因子：
14.5
作者：
Gelfand, Jeffrey M.;Nolan, Rachel;Green, Ari J.
通讯作者：
Green, Ari J.
影响因子：
158.5
作者：
Cohen, Jeffrey A.;Barkhof, Frederik;Kappos, Ludwig
通讯作者：
Kappos, Ludwig