Elwood Benjamin W, Godwin Cheyanne R, Anders Jeffrey J, Kardon Randy H, Gramlich Oliver W
Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA.
Center for the Prevention and Treatment of Visual Loss, Iowa City Veterans Affairs Health Care System, Iowa City, IA, USA.
Transl Vis Sci Technol. 2024 Aug 1;13(8):1. doi: 10.1167/tvst.13.8.1.
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.
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.
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.
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.
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.
实验性自身免疫性脑脊髓炎（EAE）评分是多发性硬化症（MS）体内模型最常用的主要结局指标，其具有高度变异性和主观性。在此，我们探讨了将视觉生物标志物用于EAE，作为更客观且与临床相关的主要结局指标。
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小鼠的运动功能障碍进行量化。诱导后60天测量图形视网膜电图（pERG）以及视网膜神经节细胞/内丛状层（RGC/IPL）复合体厚度。在实验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功能障碍。pERG振幅与末次EAE评分、平均EAE评分和累积EAE评分之间存在显著相关性。光学相干断层扫描（OCT）分析表明，RGC/IPL复合体变薄与EAE评分和pERG振幅均存在显著相关性。视神经组织病理学显示，EAE小鼠的脱髓鞘与累积EAE评分、pERG振幅和RGC/IPL复合体厚度之间存在显著相关性，免疫细胞浸润与累积EAE评分、pERG振幅和RGC/IPL复合体厚度之间也存在显著相关性。
与EAE评分不同，pERG和OCT可直接测量视网膜结构和功能。因此，我们得出结论，视觉结局非常适合作为该MS的EAE模型中视神经受累情况的直接评估指标，同时也可指示运动功能障碍。
将直接可转化的测量标准化为小鼠EAE模型的主要结局参数，可能会使缓解MS的新治疗方法的测试更加快速且相关。
