In vivo gene expression profiling of retina postintravitreal injections of dexamethasone and triamcinolone at clinically relevant time points for patient care.
In vivo gene expression profiling of retina postintravitreal injections of dexamethasone and triamcinolone at clinically relevant time points for patient care.
复制标题
在患者护理的临床相关时间点玻璃体内注射地塞米松和曲安西龙后视网膜的体内基因表达谱。
DOI：
10.1167/iovs.10-7084
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发表时间：
2011
影响因子：
4.4
通讯作者：
Morse,LawrenceS
中科院分区：
文献类型：
--
作者：
Smit-McBride,Zeljka;Modjtahedi,SaraP;Cessna,ChristopherT;Telander,DavidG;Hjelmeland,LeonardM;Morse,LawrenceS
目的：为了鉴定视网膜基因及其相关表达途径，在临床相关时间点在小鼠中玻璃体内注射地塞米松（Dex）和曲安奈德（TAA）以用于患者护理。在玻璃体内类固醇注射后1周和1个月的时间点，使用小鼠基因组微阵列分析了6周龄C57 BL/6 J小鼠视网膜中超过34，000个良好表征的小鼠基因的差异基因表达。使用商业微阵列分析软件分析数据，以获得基因表达途径中的生物学相关变化。一个共同的基因途径，与差异激活基因的类固醇和时间点，是“脑信号蛋白信号在神经元”，一个成员的“轴突导向信号系统”。注射后1周，共同的主题是视网膜胶质细胞、肿瘤坏死因子-α和转化生长因子-β信号通路中表达的基因激活，应激反应蛋白（Serpina 3 n、Cebpd）以及神经肽信号传导生长抑素受体（Sstr 2）上调。Dex的独特之处在于急性期蛋白（GFAP，Cp，Edn 2）以及Plexna 2（一种脑信号蛋白信号受体）的上调，而EphrinB受体ephexin 1（Argef 15）下调。叶酸信号似乎是唯一的TAA在1周（Folh 1，Cubn），而芳基烃受体信号可能是重要的类固醇在1个月后注射。结论：了解眼内类固醇治疗的分子和遗传效应具有临床意义。这项体内研究阐明了几种基因和途径，这些基因和途径可能会改变玻璃体内类固醇治疗期间神经胶质细胞和视网膜神经节细胞之间的神经保护/神经退行性平衡。
Purpose.: To identify retinal genes and their relevant expression pathways affected by intravitreal injections of dexamethasone (Dex) and triamcinolone acetonide (TAA) in mice at clinically relevant time points for patient care.Methods.: Differential gene expressions of over 34,000 well-characterized mouse genes, in the retinas of 6-week-old C57BL/6J mice, were analyzed after intravitreal steroid injections at 1 week and 1 month time points, using mouse genome microarrays. The data were analyzed using commercial microarray analysis software for biologically relevant changes in gene expression pathways.Results.: A common gene pathway, with differentially activated genes for both steroids and time points, was “Semaphorin Signaling in Neurons,” a member of the “Axonal Guidance Signaling System.” At 1 week postinjection a common theme was activation of genes expressed in retinal glial cells, tumor necrosis factor-α, and transforming growth factor-β signaling pathways and upregulation of stress response proteins (Serpina3n, Cebpd), as well as neuropeptide signaling somatostatin receptor (Sstr2). Unique for Dex was the upregulation of acute phase proteins (Gfap, Cp, Edn2) as well as Plexna2, a semaphorin signaling receptor, whereas EphrinB receptor ephexin 1 (Argef15) was downregulated. Folate signaling appears to be unique for TAA at 1 week (Folh1, Cubn), whereas aryl-hydrocarbon receptor signaling might be important for both steroids at 1 month postinjection.Conclusions.: Understanding the molecular and genetic effects of intraocular steroid treatments is of clinical relevance. This in vivo study has elucidated several genes and pathways that are potentially altering the neuroprotective/neurodegenerative balance between glial and retinal ganglion cells during intravitreal steroid treatment.