Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA, United States of America.
Culver Vision Discovery Institute, Augusta University, Augusta, GA, United States of America.
PLoS One. 2021 Mar 18;16(3):e0247901. doi: 10.1371/journal.pone.0247901. eCollection 2021.
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.
视神经炎(ON)导致的视力障碍是多发性硬化症(MS)的主要临床表现之一,其特征为视神经和视网膜的炎症和变性。目前可用的治疗方法仅部分有效,对疾病的神经炎症病理影响有限。我们实验室最近的一项研究强调了精氨酸酶 2(A2)缺失在抑制 MS 实验模型中视网膜神经退行性变和炎症方面的有益作用。利用相同的模型,本研究调查了 A2 缺乏对 MS 诱导的视神经炎的影响。在野生型(WT)和 A2 敲除(A2-/-)小鼠中诱导实验性自身免疫性脑脊髓炎(EAE)。A2-/-视神经中的 EAE 诱导的细胞浸润以及小胶质细胞和巨噬细胞的激活减少。EAE 视神经中的轴突变性和脱髓鞘现象观察到随着 A2 缺失而减少。此外,缺乏 A2 可显著改善 EAE 诱导的星形胶质细胞增生。总之,我们的研究结果表明精氨酸酶 2在介导视神经炎中的神经炎症中起关键作用,并提示 A2 阻断作为 MS 诱导的视神经炎的靶向治疗的潜力。