转基因报告小鼠实验性自身免疫性葡萄膜视网膜炎的体内多模态成像揭示了疾病进展过程中炎症变化的动态性质。
In vivo multi-modal imaging of experimental autoimmune uveoretinitis in transgenic reporter mice reveals the dynamic nature of inflammatory changes during disease progression.
作者信息
Chen Xiangting, Kezic Jelena M, Forrester John V, Goldberg Gabrielle L, Wicks Ian P, Bernard Claude C, McMenamin Paul G
机构信息
Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
Section of Immunology and Infection, Division of Applied Medicine, School of Medicine and Dentistry, Institute of Medical Science, Foresterhill, University of Aberdeen, Scotland, UK.
出版信息
J Neuroinflammation. 2015 Jan 27;12:17. doi: 10.1186/s12974-015-0235-6.
BACKGROUND
Experimental autoimmune uveoretinitis (EAU) is a widely used experimental animal model of human endogenous posterior uveoretinitis. In the present study, we performed in vivo imaging of the retina in transgenic reporter mice to investigate dynamic changes in exogenous inflammatory cells and endogenous immune cells during the disease process.
METHODS
Transgenic mice (C57Bl/6 J Cx 3 cr1 (GFP/+) , C57Bl/6 N CD11c-eYFP, and C57Bl/6 J LysM-eGFP) were used to visualize the dynamic changes of myeloid-derived cells, putative dendritic cells and neutrophils during EAU. Transgenic mice were monitored with multi-modal fundus imaging camera over five time points following disease induction with the retinal auto-antigen, interphotoreceptor retinoid binding protein (IRBP1-20). Disease severity was quantified with both clinical and histopathological grading.
RESULTS
In the normal C57Bl/6 J Cx 3 cr1 (GFP/+) mouse Cx3cr1-expressing microglia were evenly distributed in the retina. In C57Bl/6 N CD11c-eYFP mice clusters of CD11c-expressing cells were noted in the retina and in C57Bl/6 J LysM-eGFP mice very low numbers of LysM-expressing neutrophils were observed in the fundus. Following immunization with IRBP1-20, fundus examination revealed accumulations of Cx3cr1-GFP(+) myeloid cells, CD11c-eYFP(+) cells and LysM-eGFP(+) myelomonocytic cells around the optic nerve head and along retinal vessels as early as day 14 post-immunization. CD11c-eYFP(+) cells appear to resolve marginally earlier (day 21 post-immunization) than Cx3cr1-GFP(+) and LysM-eGFP(+) cells. The clinical grading of EAU in transgenic mice correlated closely with histopathological grading.
CONCLUSIONS
These results illustrate that in vivo fundus imaging of transgenic reporter mice allows direct visualization of various exogenously and endogenously derived leukocyte types during EAU progression. This approach acts as a valuable adjunct to other methods of studying the clinical course of EAU.
背景
实验性自身免疫性葡萄膜视网膜炎（EAU）是一种广泛应用的人类内源性后葡萄膜视网膜炎的实验动物模型。在本研究中，我们对转基因报告小鼠的视网膜进行了体内成像，以研究疾病过程中外源性炎症细胞和内源性免疫细胞的动态变化。
方法
使用转基因小鼠（C57Bl/6 J Cx 3 cr1(GFP/+)、C57Bl/6 N CD11c-eYFP和C57Bl/6 J LysM-eGFP）来观察EAU期间髓系来源细胞、假定树突状细胞和中性粒细胞的动态变化。在用视网膜自身抗原光感受器间维生素A结合蛋白（IRBP1-20）诱导疾病后，通过多模态眼底成像相机在五个时间点对转基因小鼠进行监测。通过临床和组织病理学分级对疾病严重程度进行量化。
结果
在正常的C57Bl/6 J Cx 3 cr1(GFP/+)小鼠中，表达Cx3cr1的小胶质细胞均匀分布在视网膜中。在C57Bl/6 N CD11c-eYFP小鼠的视网膜中发现了表达CD11c的细胞簇，在C57Bl/6 J LysM-eGFP小鼠的眼底观察到表达LysM的中性粒细胞数量非常少。在用IRBP1-20免疫后，眼底检查显示早在免疫后第14天，视神经乳头周围和沿视网膜血管就有Cx3cr1-GFP(+)髓系细胞、CD11c-eYFP(+)细胞和LysM-eGFP(+)髓单核细胞聚集。CD11c-eYFP(+)细胞似乎比Cx3cr1-GFP(+)和LysM-eGFP(+)细胞更早（免疫后第2天）消退。转基因小鼠中EAU的临床分级与组织病理学分级密切相关。
结论
这些结果表明，转基因报告小鼠的体内眼底成像可以直接观察到EAU进展过程中各种外源性和内源性来源的白细胞类型。这种方法是研究EAU临床过程的其他方法的有价值的辅助手段。
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