Retinal ganglion cell damage induced by spontaneous autoimmune optic neuritis in MOG-specific TCR transgenic mice
Retinal ganglion cell damage induced by spontaneous autoimmune optic neuritis in MOG-specific TCR transgenic mice
复制标题
MOG 特异性 TCR 转基因小鼠自发性自身免疫性视神经炎引起的视网膜神经节细胞损伤
DOI：
10.1016/j.jneuroim.2006.05.019
复制
发表时间：
2006-09-01
影响因子：
3.3
通讯作者：
Rostami, A. M.
中科院分区：
文献类型：
--
作者：
Guan, Yangtai;Shindler, Kenneth S.;Rostami, A. M.
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）以包括视神经在内的整个中枢神经系统的炎性脱髓鞘病变为标志。EAE中也发生神经元损失，包括视神经炎眼中的视网膜神经节细胞（RGC）损失，但在不同的EAE环境中，与视神经炎症相关的RGC损失的发现不同。最近，髓鞘少突胶质细胞糖蛋白（MOG）特异性TCR转基因小鼠被发现在没有EAE的情况下发生自发性孤立性视神经炎。在目前的研究中，炎症与视网膜神经节细胞（RGC）损失孤立性视神经炎的关系进行了检查。用荧光金标记MOG特异性TCR转基因小鼠的RGC，然后用百日咳毒素（PT）处理或观察未处理。在不同的时间点，对RGC进行计数，对视网膜进行TUNEL标记，并检查视神经的炎性细胞浸润。29%的未处理的MOG特异性TCR转基因小鼠在4月龄时发生眼周炎症，并且TCR转基因小鼠的32%的视神经在视神经中具有组织学病变。组织学视神经炎的发生率在注射PT后第8天为20%，到第12天增加到48%，到第16天增加到68%。相比之下，在注射PT的小鼠中，直到第12天，在患有视神经炎的眼睛中未检测到RGC损失或TUNEL染色。在第12天RGC数量减少28%，到第16天增加到39%，并且具有严重或大量炎症的眼睛的RGC损失显著高于具有轻度或中度炎症的眼睛。在无视神经炎的TCR转基因小鼠眼中没有发生RGC丢失。炎症先于RGC损失的事实表明，视神经炎期间的神经元损失继发于孤立性视神经炎的炎症过程。(c)2006 Elsevier B.V.保留所有权利。
Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are marked by inflammatory demyelinating lesions throughout the central nervous system, including optic nerve. Neuronal loss also occurs in EAE, including retinal ganglion cell (RGC) loss in eyes with optic neuritis, but the finding of RGC loss in relation to optic nerve inflammation differs in different EAE settings. Recently, Myelin oligodendrocyte glycoprotein (MOG)-specific TCR transgenic mice were found to develop spontaneous isolated optic neuritis in the absence of EAE. In the current study, the relationship of inflammation to retinal ganglion cell (RGC) loss during isolated optic neuritis is examined. RGCs of MOG-specific TCR transgenic mice were labeled with Flourogold and then treated with pertussis toxin (PT) or observed untreated. At various time points, RGCs were counted, retinas were TUNEL labeled, and optic nerves were examined for inflammatory cell infiltrates. 29% of untreated MOG-specific TCR transgenic mice developed periocular inflammation by 4 months of age, and 32% of optic nerves of TCR transgenic mice had histological lesions in the optic nerve. Incidence of histological optic neuritis was 20% at day 8 following injection of PT and increased to 48% by day 12, and 68% by day 16. In contrast, no RGC loss or TUNEL staining was detected in eyes with optic neuritis until day 12 in the mice injected with PT. A 28% reduction in RGC numbers at day 12 increased to 39% by day 16, and RGC loss of eyes with severe or massive inflammation was significantly higher than that of eyes with mild or moderate inflammation. No RGC loss occurred in TCR transgenic mouse eyes without optic neuritis. The fact that inflammation precedes RGC loss suggests that neuronal loss during optic neuritis occurs secondary to the inflammatory process in isolated optic neuritis. (c) 2006 Elsevier B.V. All rights reserved.