Marenna Silvia, Huang Su-Chun, Castoldi Valerio, d'Isa Raffaele, Costa Gloria Dalla, Comi Giancarlo, Leocani Letizia
Experimental Neurophysiology Unit, Institute of Experimental Neurology-INSPE, IRCCS San Raffaele Hospital, Milan, Italy.
Mult Scler J Exp Transl Clin. 2020 Oct 28;6(4):2055217320963474. doi: 10.1177/2055217320963474. eCollection 2020 Oct-Dec.
Experimental autoimmune encephalomyelitis (EAE) is a common animal model of multiple sclerosis (MS). C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein exhibit chronic disease course, together with optic neuritis, consisting of demyelination/axonal loss of the optic nerve.
To characterize functional and structural visual damages in two different phases of EAE: pre- and post-motor onset.
Visual alterations were detected with Visual Evoked Potential (VEP), Electroretinogram (ERG) and Optical Coherence Tomography (OCT). Optic nerve histology was performed at 7 (pre-motor onset) or 37 (post-motor onset) days post-immunization (dpi).
At 7 dpi, optic nerve inflammation was similar in EAE eyes with and without VEP latency delay. Demyelination was detected in EAE eyes with latency delay (p < 0.0001), while axonal loss (p < 0.0001) and ERG b-wave amplitude (p = 0.004) were decreased in EAE eyes without latency delay compared to Healthy controls. At 37 dpi, functional and structural optic nerve damage were comparable between EAE groups, while a decrease of ERG amplitude and NGCC thickness were found in EAE eyes with VEP latency delay detected post-motor onset.
Thanks to non-invasive methods, we studied the visual system in a MS model, which could be useful for developing specific therapeutic strategies to target different disease phases.
实验性自身免疫性脑脊髓炎(EAE)是多发性硬化症(MS)的常见动物模型。用髓鞘少突胶质细胞糖蛋白免疫的C57BL/6小鼠表现出慢性病程,并伴有视神经炎,包括视神经的脱髓鞘/轴突损失。
表征EAE两个不同阶段(运动发作前和运动发作后)的功能性和结构性视觉损伤。
用视觉诱发电位(VEP)、视网膜电图(ERG)和光学相干断层扫描(OCT)检测视觉改变。在免疫后7天(运动发作前)或37天(运动发作后)进行视神经组织学检查。
在免疫后7天,有和没有VEP潜伏期延迟的EAE眼睛的视神经炎症相似。在有潜伏期延迟的EAE眼睛中检测到脱髓鞘(p<0.0001),而与健康对照相比,没有潜伏期延迟的EAE眼睛的轴突损失(p<0.0001)和ERG b波振幅(p=0.004)降低。在免疫后37天,EAE组之间的功能性和结构性视神经损伤相当,而在运动发作后检测到有VEP潜伏期延迟的EAE眼睛中发现ERG振幅和神经节细胞复合体厚度降低。
借助非侵入性方法,我们在MS模型中研究了视觉系统,这可能有助于制定针对不同疾病阶段的特定治疗策略。