The alarmin IL-33 amplifies an immune response in the degenerating retina

ST2 heterodimerizes with IL-1RAcp to form the receptor for IL-33, which is primarily associated with allergic inflammation by inducing Th2 responses. Recently, however, IL-33 was found to be expressed in the central nervous system and in retinal Muller cells which imply functions, as yet undescribed, beyond Th2 mediated inflammation. Muller cells support the health of the retina and photoreceptors and are also involved in inflammation in retinal degeneration. It is not known how IL-33/ST2 functions in this capacity. We recently found that ST2 ko mice are protected from CLE-induced photoreceptor loss, implying a detrimental effect of IL33/ST2 in CLE. We wish to perform microarray analysis using WT and ST2 KO mice in CLE model to better understand the mechanism by which IL-33/ST2 regulates retinal degeneration. CLE (Constant Light Exposure) is a model of retinal damage/degeneration in mice. Mice are exposed to bright light 24 hours a day for a period of time which damages retina photoreceptors. This damage is assessed by histology, optical coherence tomography (OCT), which measures retina thickness in vivo. In this experiment, the WT and ST2 KO mice (5 mice per genotype per time point) will be exposed to 1200-lux constant light for 0, 3, 10 days. The retinal RNA will be isolated and analyzed for differential gene expression by microarray.ST2可与IL-1RAcp形成异二聚体，构成IL-33的功能性受体，该通路主要通过诱导Th2型免疫应答参与变应性炎症的发生。然而近期研究发现，IL-33在中枢神经系统及视网膜穆勒细胞（Muller cells）中均有表达，这提示其可能存在尚未被阐明的、不依赖于Th2型炎症的生物学功能。穆勒细胞可维持视网膜及光感受器的健康，同时也参与视网膜变性过程中的炎症反应。目前尚不明确IL-33/ST2通路在此过程中的具体作用机制。我们近期的研究发现，ST2基因敲除（ST2 KO）小鼠可免受CLE诱导的光感受器丢失，这提示IL-33/ST2通路在CLE模型中发挥有害作用。本研究拟在CLE模型中利用野生型（WT）及ST2 KO小鼠开展基因芯片（microarray）分析，以进一步阐明IL-33/ST2通路调控视网膜变性的具体分子机制。CLE（恒定光照暴露，Constant Light Exposure）是小鼠视网膜损伤/变性的经典动物模型。实验小鼠将被每日24小时持续暴露于强光环境，持续指定时长以诱导视网膜光感受器损伤。该视网膜损伤可通过组织病理学检测、光学相干断层扫描（optical coherence tomography, OCT）进行评估，其中OCT可实现视网膜厚度的在体测量。本实验中，野生型（WT）及ST2 KO小鼠（每个基因型每个时间点设置5只）将被暴露于1200勒克斯的恒定光照环境，处理时长分别为0天、3天及10天。随后将提取视网膜组织总RNA，通过基因芯片分析其差异基因表达情况。