Dynamic Changes of microRNAs in the Eye during the Development of Experimental Autoimmune Uveoretinitis
Dynamic Changes of microRNAs in the Eye during the Development of Experimental Autoimmune Uveoretinitis
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DOI：
10.1167/iovs.10-6115
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发表时间：
2011-01-01
影响因子：
4.4
通讯作者：
Fukushima, Atsuki
中科院分区：
文献类型：
--
作者：
Ishida, Waka;Fukuda, Ken;Fukushima, Atsuki
目的。产生白介素 (IL)-17 的 Th17 细胞在实验性自身免疫性葡萄膜视网膜炎 (EAU) 的发展中发挥着至关重要的作用。最近的研究表明，IL-17 等细胞因子的产生是由 microRNA (miRNA) 控制的。在此，作者研究了 EAU 开发过程中眼睛中 miRNA 的表达。方法。为了诱导EAU，B10.RIII小鼠注射光感受器间视黄醇结合蛋白肽161-180和佐剂。对照小鼠仅接受佐剂。免疫后 7、14、21 或 28 天，采集眼睛进行组织学分析、miRNA 阵列、细胞因子和 miRNA 的定量实时聚合酶链反应 (qRT-PCR) 以及 miRNA 的原位杂交。细胞因子和 miRNA 的表达水平与对照小鼠进行比较。结果。第7天收集的眼睛没有观察到组织学变化。第14天，EAU最严重，此后视网膜结构逐渐被破坏。在对照小鼠中未观察到视网膜炎症。第 7 天，EAU 诱导小鼠眼中的 IL-17A 和 IL-17F 显着升高。qRT-PCR 后的阵列分析显示，在 EAU 诱导小鼠中，miRNA-142-5p 和 miRNA-21 显着升高，而 miRNA-182 显着降低。这些变化可以在 EAU 诱导后 7 天检测到。这些 miRNA 的原位杂交分析证实了 qRT-PCR 数据。结论。在组织学 EAU 之前，可以在眼睛中检测到三种 miRNA 的表达变化。这些 miRNA 在眼睛中的动力学变化与 IL-17 的动力学变化相似。 miRNA 可能影响 IL-17，表明视网膜中的 miRNA 调节 EAU 的发育。 （投资眼科可见科学。2011；52：611-617）DOI：10.1167/iovs.10-6115
PURPOSE. Interleukin (IL)-17-producing Th17 cells play a crucial role in the development of experimental autoimmune uveoretinitis (EAU). Recent studies revealed that the production of cytokines such as IL-17 is controlled by microRNA (miRNA). Here the authors investigated the expression of miRNA in the eye during the development of EAU.METHODS. To induce EAU, B10.RIII mice were injected with interphotoreceptor retinoid binding protein peptide 161-180 with adjuvants. Control mice received adjuvants alone. Seven, 14, 21, or 28 days after immunization, eyes were harvested for histologic analysis, miRNA array, quantitative real-time polymerase chain reaction (qRT-PCR) for cytokines and miRNAs, and in situ hybridization for miRNAs. Expression levels of cytokines and miRNAs were compared with control mice.RESULTS. No histologic changes were observed in eyes collected at day 7. At day 14, EAU was most severe, and thereafter retinal structure was gradually destroyed. Retinal inflammation was not observed in control mice. IL-17A and IL-17F were significantly higher in the eyes of EAU-induced mice at day 7. Array analysis followed by qRT-PCR revealed that in EAU-induced mice, miRNA-142-5p and miRNA-21 were significantly higher, whereas miRNA-182 was significantly lower. These changes could be detected 7 days after EAU induction. In situ hybridization analysis for these miRNAs confirmed qRT-PCR data.CONCLUSIONS. Expression changes in three miRNAs could be detected in the eye before histologic EAU. Kinetic changes of these miRNAs in the eye paralleled those of IL-17. The possibility that miRNAs can affect IL-17 suggests that miRNAs in the retina regulate the development of EAU. (Invest Ophthalmol Vis Sci. 2011;52:611-617) DOI:10.1167/iovs.10-6115