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白细胞介素4导致视网膜中信号转导和转录激活因子6(STAT6)及细胞外信号调节激酶(ERK)通路的持续磷酸化,并破坏啮齿动物的皮质下视觉回路。

Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents.

作者信息

Goulart Vanessa Gama, Menezes Grasielle Duarte, Espírito-Santo Sheila, Faria-Melibeu Adriana da Cunha, Serfaty Claudio Alberto, Campello-Costa Paula

出版信息

Neuroimmunomodulation. 2018;25(2):96-102. doi: 10.1159/000490895. Epub 2018 Aug 15.

DOI:10.1159/000490895
PMID:30110698
Abstract

OBJECTIVE

Interleukin 4 (IL-4) is an anti-inflammatory cytokine related to different aspects of central nervous system development such as survival, proliferation, and differentiation, among others. Our goals were to investigate the effect of intravitreous treatment with IL-4 on the activation of downstream signaling pathways in the retina and the distribution of retinal axons within the superior colliculus (SC).

MATERIAL AND METHODS

Lister hooded rats were submitted to an intravitreous injection of either IL-4 (5 U/µL) or PBS (vehicle) at postnatal day 10 (PND10). At PND11 or PND14, retinas were processed for Western blot or immunohistochemistry. At PND13, a group of animals received an intraocular injection of an anterograde tracer in the left (untreated) eye in order to label the uncrossed retinotectal axons.

RESULTS

Our data revealed that intravitreous treatment with IL-4 at PND10 leads to a decrease in GFAP content and a sustained increase in the phosphorylation of STAT6 and ERK levels in the retina. IL-4 also increases retinal axonal arbors within the SC, compared to control groups.

CONCLUSIONS

These data suggest that a single in vivo treatment with IL-4 during the early stages of development modulates signaling pathways in the retina, resulting in altered binocular subcortical visual connectivity.

摘要

目的

白细胞介素4(IL-4)是一种抗炎细胞因子,与中枢神经系统发育的不同方面相关,如存活、增殖和分化等。我们的目标是研究玻璃体内注射IL-4对视网膜下游信号通路激活以及视网膜轴突在上丘(SC)内分布的影响。

材料与方法

在出生后第10天(PND10),对利斯特戴帽大鼠进行玻璃体内注射,分别注射IL-4(5 U/µL)或PBS(溶剂对照)。在PND11或PND14,对视网膜进行蛋白质免疫印迹或免疫组织化学处理。在PND13,一组动物在左眼(未处理眼)进行眼内注射顺行示踪剂,以标记未交叉的视网膜顶盖轴突。

结果

我们的数据显示,在PND10进行玻璃体内注射IL-4会导致视网膜中GFAP含量降低,STAT6磷酸化和ERK水平持续升高。与对照组相比,IL-4还增加了SC内的视网膜轴突分支。

结论

这些数据表明,在发育早期进行单次体内注射IL-4可调节视网膜中的信号通路,从而导致双眼皮质下视觉连接改变。

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