State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University (SYSU), Guangzhou, 510060, China.
Curr Mol Med. 2018;18(9):602-611. doi: 10.2174/1566524019666190112132610.
Experimental autoimmune uveitis (EAU) represents autoimmune uveitis in humans, among which B10.RIII and C57BL/6 are the frequently used strains in mice, but to date, no study has been reported to compare EAU disease between the two strains. Here we compared the differences in morphology, pathology, visual function of the retinal inflammation and Th1/Th17 immune responses in the EAU models induced by the interphotoreceptor retinoid binding protein (IRBP) between the B10.RIII and C57BL/6 strains, using fundus and histological examinations, optical coherence tomography, electroretinography and immunoassays.
EAU induced in B10.RIII mice exhibited a shortterm severe inflammation with massive ocular infiltrates of inflammatory cells and extensive destruction of the retina that culminated in rapid degeneration of the retina and permanent loss of visual function. In contrast, C57BL/6 mice developed chronic inflammation with recurring and persistent retinitis for several months, highlighting moderate scores of disease severity and visual signal in comparison with those in B10.RIII mice. Consistent with the clinical manifestations, increased Th1/Th17 effector responses were detected in the uveitic eyes of B10.RIII strain than those in C57BL/6 strain. These data demonstrate distinguishing features of retinal inflammation and T-cell immune responses involved in IRBP-induced EAU between B10.RIII and C57BL/6 strains.
Our findings suggest that the persistent-recurring EAU model induced in C57BL/6 mice may serve as a better tool to represent distinct aspects of human uveitis.
实验性自身免疫性葡萄膜炎(EAU)代表了人类的自身免疫性葡萄膜炎,其中 B10.RIII 和 C57BL/6 是小鼠中常用的品系,但迄今为止,尚无研究报道比较这两种品系的 EAU 疾病。在这里,我们比较了 B10.RIII 和 C57BL/6 品系之间由间视网膜视黄醇结合蛋白(IRBP)诱导的 EAU 模型在形态、病理学、视网膜炎症的视觉功能以及 Th1/Th17 免疫反应方面的差异,使用眼底和组织学检查、光学相干断层扫描、视网膜电图和免疫测定。
B10.RIII 小鼠诱导的 EAU 表现为短期严重炎症,大量眼内炎症细胞浸润和视网膜广泛破坏,导致视网膜迅速退化和视觉功能永久丧失。相比之下,C57BL/6 小鼠发生慢性炎症,持续数月反复发作性视网膜炎,与 B10.RIII 小鼠相比,疾病严重程度和视觉信号评分适中。与临床表现一致,在 B10.RIII 品系的葡萄膜炎眼中检测到 Th1/Th17 效应反应增加,而在 C57BL/6 品系中则没有。这些数据表明,在 B10.RIII 和 C57BL/6 品系之间,IRBP 诱导的 EAU 中存在不同的视网膜炎症和 T 细胞免疫反应特征。
我们的研究结果表明,C57BL/6 小鼠中诱导的持续性复发性 EAU 模型可能成为代表人类葡萄膜炎不同方面的更好工具。