Comprehensive gene-expression profile in murine oxygen-induced retinopathy
Comprehensive gene-expression profile in murine oxygen-induced retinopathy
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DOI：
10.1136/bjo.2008.142646
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发表时间：
2008-10
影响因子：
4.1
通讯作者：
Tatsuhiko Sato;S. Kusaka;N. Hashida;Y. Saishin;T. Fujikado;Y. Tano
中科院分区：
文献类型：
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作者：
Tatsuhiko Sato;S. Kusaka;N. Hashida;Y. Saishin;T. Fujikado;Y. Tano
背景/目标：探讨小鼠氧诱导视网膜病变（OIR）的临床过程和基因表达模式之间的相关性，OIR是早产儿视网膜病变（ROP）的常用模型。方法：通过将出生后第7天（P7）的幼崽置于75%氧气中5天，在C57 BL/6 N小鼠中诱导OIR。从P12到P21，在荧光素异硫氰酸酯结合的葡聚糖灌注后，在视网膜平片上评价OIR的临床过程。从P12到P21，每天用TaqMan低密度阵列（TLDA）通过RT-PCR测定通过微阵列分析选择的94个基因的表达值，并进行分层聚类分析。结果：TLDA聚类分析显示，P12与P13、P16与P17基因表达模式具有同源性。许多与炎症相关的基因在P12和P13时上调，此时中央无血管区和中央血管收缩的程度都是最大的，并且这些基因的上调持续到P21。在P16和P17，当视网膜外新生血管形成变得最明显时，与血管生成相关的几个基因，例如，血管内皮生长因子-A和血管生成素-2，上调最多。结论：该基因表达模式与小鼠OIR的临床表现有很好的相关性，这些发现有助于了解ROP的病理状态。
Background/aims: To investigate the correlation between the clinical course and gene-expression pattern in murine oxygen-induced retinopathy (OIR), a commonly used model of retinopathy of prematurity (ROP). Methods: OIR was induced in C57BL/6N mice by placing postnatal day 7 (P7) pups in 75% oxygen for 5 days. The clinical course of the OIR was evaluated on retinal flat-mounts after fluorescein isothiocyanate-conjugated dextran perfusion from P12 to P21. The expression values of 94 genes, selected by microarray analyses, were determined daily from P12 through P21 by RT-PCR with TaqMan low-density array (TLDA) and analysed by hierarchical clustering. Results: TLDA cluster analyses showed a homology of gene-expression pattern between P12 and P13 and between P16 and P17. Many genes associated with inflammation were upregulated on P12 and P13 when the degree of both central avascular area and central vasoconstriction were maximal, and the upregulation of the genes continued to P21. At P16 and P17 when extraretinal neovascularisation became most noticeable, several genes associated with angiogenesis, for example, vascular endothelial growth factor-A and angiopoietin-2, were most upregulated. Conclusion: The gene-expression pattern was well correlated with the clinical appearance in murine OIR. These findings should contribute to the understanding of the pathological conditions in ROP.