Smit-McBride Zeljka, Moisseiev Elad, Modjtahedi Sara P, Telander David G, Hjelmeland Leonard M, Morse Lawrence S
Vitreoretinal Research Laboratory, UC Davis Department of Ophthalmology, Davis, CA 95616, USA.
Vitreoretinal Research Laboratory, UC Davis Department of Ophthalmology, Davis, CA 95616, USA; Department of Ophthalmology and Visual Science, UC Davis Medical Center, 4860 Y Street, Suite 2400, Sacramento, CA 95817, USA.
J Ophthalmol. 2016;2016:9856736. doi: 10.1155/2016/9856736. Epub 2016 Jun 27.
Purpose. To identify retinal pigment epithelium (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. Methods. Differential gene expression of over 34,000 well-characterized mouse genes in the RPE/choroid of 6-week-old C57BL/6J mice was analyzed after intravitreal steroid injections at 1 week and 1 month postinjection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpring GX 12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. Results. Both triamcinolone and dexamethasone caused differential activation of genes involved in "Circadian Rhythm Signaling" pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in "Calcium Signaling" (1 week) and "Glutamate Receptor Signaling" pathways (1 month). In contrast, dexamethasone (Dex) affected the "GABA Receptor Signaling" (1 week) and "Serotonin Receptor Signaling" (1 month) pathways. Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. Conclusions. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina.
目的。在与患者护理相关的临床时间点,确定玻璃体内注射地塞米松和曲安奈德对小鼠视网膜色素上皮(RPE)/脉络膜基因及其相关表达途径的影响。方法。在6周龄C57BL/6J小鼠玻璃体内注射类固醇1周和1个月后,使用Affymetrix Mouse Genome 430 2.0微阵列分析RPE/脉络膜中34000多个特征明确的小鼠基因的差异基因表达。使用GeneSpring GX 12.5和Ingenuity Pathway Analysis(IPA)微阵列分析软件对数据进行生物学相关变化分析。结果。在两个测试时间点,曲安奈德和地塞米松均导致参与“昼夜节律信号”途径的基因发生差异激活。曲安奈德(TAA)在“钙信号”(1周)和“谷氨酸受体信号”途径(1个月)中独特地诱导了基因表达的显著变化。相比之下,地塞米松(Dex)影响“GABA受体信号”(1周)和“5-羟色胺受体信号”(1个月)途径。了解眼内类固醇如何影响RPE/脉络膜的基因表达具有临床相关性。结论。这项体内研究阐明了在玻璃体内注射类固醇期间,RPE/脉络膜中可能改变昼夜节律以及其他几种神经递质途径的几个基因和途径,这可能会导致RPE功能失调和视网膜神经变性。