PDF(Pubmed)
Abstract：
UNASSIGNED: Experimental autoimmune encephalomyelitis (EAE) scoring, the most commonly used primary outcome metric for an in vivo model of multiple sclerosis (MS), is highly variable and subjective. Here we explored the use of visual biomarkers in EAE as more objective and clinically relevant primary outcomes.
UNASSIGNED: Motor impairment in myelin oligodendrocyte glycoprotein-immunized C57BL/6J mice was quantified using a five-point EAE grading scale. Pattern electroretinography (pERG) and retinal ganglion cell/inner plexiform layer (RGC/IPL) complex thickness were measured 60 days after induction. Optic nerve histopathology was analyzed at endpoint.
UNASSIGNED: EAE mice displayed motor impairments ranging from mild to severe. Significant correlations were seen between pERG amplitude and last EAE score, mean EAE score, and cumulative EAE score. Optical coherence tomography (OCT) analysis demonstrated a significant correlation between thinning of the RGC/IPL complex and both EAE score and pERG amplitude. Optic nerve histopathology showed significant correlations between demyelination and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness, as well as between immune cell infiltration and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness in EAE mice.
UNASSIGNED: Unlike EAE scoring, pERG and OCT show direct measurement of retinal structure and function. Therefore we conclude that visual outcomes are well suited as a direct assessment of optic nerve involvement in this EAE model of MS while also being indicative of motor impairment.
UNASSIGNED: Standardizing directly translatable measurements as primary outcome parameters in the murine EAE model could lead to more rapid and relevant testing of new therapeutic approaches for mitigating MS.
UNASSIGNED: Motor impairment in myelin oligodendrocyte glycoprotein-immunized C57BL/6J mice was quantified using a five-point EAE grading scale. Pattern electroretinography (pERG) and retinal ganglion cell/inner plexiform layer (RGC/IPL) complex thickness were measured 60 days after induction. Optic nerve histopathology was analyzed at endpoint.
UNASSIGNED: EAE mice displayed motor impairments ranging from mild to severe. Significant correlations were seen between pERG amplitude and last EAE score, mean EAE score, and cumulative EAE score. Optical coherence tomography (OCT) analysis demonstrated a significant correlation between thinning of the RGC/IPL complex and both EAE score and pERG amplitude. Optic nerve histopathology showed significant correlations between demyelination and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness, as well as between immune cell infiltration and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness in EAE mice.
UNASSIGNED: Unlike EAE scoring, pERG and OCT show direct measurement of retinal structure and function. Therefore we conclude that visual outcomes are well suited as a direct assessment of optic nerve involvement in this EAE model of MS while also being indicative of motor impairment.
UNASSIGNED: Standardizing directly translatable measurements as primary outcome parameters in the murine EAE model could lead to more rapid and relevant testing of new therapeutic approaches for mitigating MS.
摘要：
■实验性自身免疫性脑脊髓炎（EAE）评分，多发性硬化症(MS)体内模型最常用的主要结果指标，是高度可变和主观的。在这里，我们探讨了视觉生物标志物在EAE中的应用，作为更客观和临床相关的主要结果。
■使用五点EAE分级量表对髓鞘少突胶质细胞糖蛋白免疫的C57BL/6J小鼠的运动障碍进行定量。诱导后60天测量模式视网膜电图（pERG）和视网膜神经节细胞/内网状层（RGC/IPL）复合物的厚度。在终点分析视神经组织病理学。
■EAE小鼠表现出从轻度到重度的运动障碍。pERG振幅与末次EAE评分之间存在显著相关性，平均EAE评分，和累积EAE评分。光学相干断层扫描（OCT）分析表明，RGC/IPL复合物的变薄与EAE评分和pERG振幅之间存在显着相关性。视神经组织病理学显示脱髓鞘与累积EAE评分之间存在显着相关性，pERG振幅，和RGC/IPL复合厚度，以及免疫细胞浸润和累积EAE评分之间，pERG振幅，和EAE小鼠的RGC/IPL复合物厚度。
■与EAE评分不同，pERG和OCT显示视网膜结构和功能的直接测量。因此，我们得出结论，视觉结果非常适合作为MSEAE模型中视神经受累的直接评估，同时也指示运动障碍。
■在鼠EAE模型中将可直接翻译的测量值标准化为主要结果参数可以导致对缓解MS的新治疗方法进行更快速和相关的测试。
■使用五点EAE分级量表对髓鞘少突胶质细胞糖蛋白免疫的C57BL/6J小鼠的运动障碍进行定量。诱导后60天测量模式视网膜电图（pERG）和视网膜神经节细胞/内网状层（RGC/IPL）复合物的厚度。在终点分析视神经组织病理学。
■EAE小鼠表现出从轻度到重度的运动障碍。pERG振幅与末次EAE评分之间存在显著相关性，平均EAE评分，和累积EAE评分。光学相干断层扫描（OCT）分析表明，RGC/IPL复合物的变薄与EAE评分和pERG振幅之间存在显着相关性。视神经组织病理学显示脱髓鞘与累积EAE评分之间存在显着相关性，pERG振幅，和RGC/IPL复合厚度，以及免疫细胞浸润和累积EAE评分之间，pERG振幅，和EAE小鼠的RGC/IPL复合物厚度。
■与EAE评分不同，pERG和OCT显示视网膜结构和功能的直接测量。因此，我们得出结论，视觉结果非常适合作为MSEAE模型中视神经受累的直接评估，同时也指示运动障碍。
■在鼠EAE模型中将可直接翻译的测量值标准化为主要结果参数可以导致对缓解MS的新治疗方法进行更快速和相关的测试。
