Camprehensive and development ct pharmacological treatment of retinopathy of prematurity

背景/目标：为探讨早产儿视网膜病变（ROP）的常见模型--小鼠氧诱导视网膜病变（OIR）的临床病程与基因表达模式之间的相关性，将出生后7天（P7）的幼鼠置于75%氧气中5天，诱导C57 BL/6 N小鼠OIR。OIR的临床过程在P12至P21期间用FITC-结合的葡聚糖灌注的视网膜平片上进行评价。结果：TLDA聚类分析显示P12与P13、P16与P17的基因表达模式具有同源性，P12与P13的基因表达模式具有同源性，P16与P17的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时表达上调，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一直持续到P21。与血管生成相关的几个代表性基因，例如，结论：视网膜外新生血管在视网膜缺血再灌注损伤中的表达与视网膜病变的临床表现密切相关，这些结果将有助于了解视网膜病变的病理机制。

Background/aims : To investigate the correlation between the clinical course and gene expression pattern in murine oxygen-induced retinopathy (OIR), a common 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 OIR was evaluated on retinal flat-mounts with FITC-conjugated dextran perfusion from P12 to P21. The expression values of 94 genes, selected by microarray analysis, were determined daily from P12 through P21 by RT-PCR with TagMan (R) low-density array (TLDA) and analyzed by hierarchical clustering.Results: TLDA cluster analysis showed the homology of gene expression pattern between P12 and P13, and between P16 and P17. Many genes associated with inflammation were up-regulated from P12 and P13, when the degrees of both central avascular area and central vasoconstriction were maximal, and the up-regulation of the genes continued to P21. Several representative genes associated with angiogenesis, e.g., vascular endothelial growth factor-A and angiopoietin-2, were most up-regulated at P16 and P17, when extraretinal neovascularization became most noticeable.Conclusion: The gene expression pattern was well-correlated with the clinical presentation in murine OIR. These findings will contribute to understand the pathological condition involved in ROP.