Optic neuritis and retinal ganglion cell loss in a chronic murine model of multiple sclerosis.
Optic neuritis and retinal ganglion cell loss in a chronic murine model of multiple sclerosis.
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DOI：
10.3389/fneur.2011.00050
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发表时间：
2011
影响因子：
3.4
通讯作者：
Shindler KS
中科院分区：
文献类型：
--
作者：
Quinn TA;Dutt M;Shindler KS
多发性硬化症（MS）及其动物模型实验性自身免疫性脑脊髓炎（EAE）是中枢神经系统（包括视神经）中具有特征性炎性脱髓鞘的神经退行性疾病。神经元和轴突损伤被认为是MS患者长期残疾的主要原因。EAE中也发生神经元丢失，包括视神经炎（ON）眼中的视网膜神经节细胞（RGC）凋亡。然而，MS和EAE的临床病程和神经元损伤水平存在显著差异。目前的研究检查了髓鞘少突胶质细胞糖蛋白免疫诱导慢性EAE疾病的C57/BL 6小鼠中RGC丢失的机制和动力学。每天对EAE的临床进展进行评分，并通过视动反应评估视力。在不同的时间点，对RGC进行计数，并检查视神经的炎性细胞浸润。几乎所有的EAE小鼠在免疫后第15天发展为ON;然而，在这些小鼠中RGC损失延迟。免疫后25天未检测到RGC损失，而与对照组相比，从免疫后35至50天，EAE小鼠中的RGC数量显著且逐渐减少。RGC损失的延迟时间过程与复发性EAE以及慢性EAE大鼠中报道的形成鲜明对比。结果表明，视神经炎症的不同临床病程可能触发不同的神经元损伤机制，或者不同啮齿动物品系中的RGCs可能对神经元变性具有可变的抗性。
Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are neurodegenerative diseases with characteristic inflammatory demyelination in the central nervous system, including the optic nerve. Neuronal and axonal damage is considered to be the main cause of long-term disability in patients with MS. Neuronal loss, including retinal ganglion cell (RGC) apoptosis in eyes with optic neuritis (ON), also occurs in EAE. However, there is significant variability in the clinical course and level of neuronal damage in MS and EAE. The current studies examine the mechanisms and kinetics of RGC loss in C57/BL6 mice immunized with myelin oligodendrocyte glycoprotein to induce a chronic EAE disease. Clinical progression of EAE was scored daily and vision was assessed by optokinetic responses. At various time points, RGCs were counted and optic nerves were examined for inflammatory cell infiltration. Almost all EAE mice develop ON by day 15 post-immunization; however, RGC loss is delayed in these mice. No RGC loss is detected 25 days post-immunization, whereas RGC numbers in EAE mice significantly and progressively decrease compared to controls from 35 to 50 days post-immunization. The delayed time course of RGC loss is in stark contrast to that reported in relapsing EAE, as well as in rats with chronic EAE. Results suggest that different clinical disease courses of optic nerve inflammation may trigger distinct mechanisms of neuronal damage, or RGCs in different rodent strains may have variable resistance to neuronal degeneration.