Comparison of gene expression profile of epiretinal membranes obtained from eyes with proliferative vitreoretinopathy to that of secondary epiretinal membranes.

Comparison of gene expression profile of epiretinal membranes obtained from eyes with proliferative vitreoretinopathy to that of secondary epiretinal membranes.
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DOI:
10.1371/journal.pone.0054191
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Ishibashi T
Ishibashi T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Asato R;Yoshida S;Ogura A;Nakama T;Ishikawa K;Nakao S;Sassa Y;Enaida H;Oshima Y;Ikeo K;Gojobori T;Kono T;Ishibashi T

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增殖性玻璃体视网膜病变(PVR)是视网膜脱离和玻璃体视网膜手术的一种破坏性并发症,可因牵引性视网膜脱离导致严重的视力下降。本研究的目的是确定与PVR相关的视网膜前膜(ERMs)的基因表达谱(PVR- erm),并将其与侵袭性较低的继发性erm的表达谱进行比较。利用玻璃体切割获得的erm中分离的rna构建了pcr扩增的互补DNA (cDNA)文库。从随机选择的克隆中获得5 '端序列,并用于生成表达序列标签(est)。我们获得了1116个非冗余簇,代表PVR-ERMs中表达的单个基因,799个簇代表次要ERMs中表达的基因。通过FatiGo分析,PVR-ERMs的转录组被细分为与代谢、细胞粘附、细胞骨架、信号传导和其他功能相关的基因的功能亚群。将pvr - erm中高表达的基因与继发性erm中表达的基因进行比较,并根据细胞粘附、增殖和其他功能对这些基因进行细分。在STRING数据库中查询10个细胞粘附相关基因,得到了70个与其他基因/蛋白可能存在的物理关系,其中包括另外60个在PVR-ERM文库中未检测到的基因。其中,可溶性CD44和可溶性血管细胞粘附分子-1在PVR患者玻璃体中显著升高。我们的研究结果支持了先前的假设,即即使从基因组的角度来看,PVR-ERM也是一种异常形式的伤口愈合反应。在PVR- erms中优先表达的基因可能在PVR的进展中起重要作用,并可能作为治疗靶点。
Proliferative vitreoretinopathy (PVR) is a destructive complication of retinal detachment and vitreoretinal surgery which can lead to severe vision reduction by tractional retinal detachments. The purpose of this study was to determine the gene expression profile of epiretinal membranes (ERMs) associated with a PVR (PVR-ERM) and to compare it to the expression profile of less-aggressive secondary ERMs. A PCR-amplified complementary DNA (cDNA) library was constructed using the RNAs isolated from ERMs obtained during vitrectomy. The sequence from the 5′ end was obtained for randomly selected clones and used to generate expressed sequence tags (ESTs). We obtained 1116 nonredundant clusters representing individual genes expressed in PVR-ERMs, and 799 clusters representing the genes expressed in secondary ERMs. The transcriptome of the PVR-ERMs was subdivided by functional subsets of genes related to metabolism, cell adhesion, cytoskeleton, signaling, and other functions, by FatiGo analysis. The genes highly expressed in PVR-ERMs were compared to those expressed in the secondary ERMs, and these were subdivided by cell adhesion, proliferation, and other functions. Querying 10 cell adhesion-related genes against the STRING database yielded 70 possible physical relationships to other genes/proteins, which included an additional 60 genes that were not detected in the PVR-ERM library. Of these, soluble CD44 and soluble vascular cellular adhesion molecule-1 were significantly increased in the vitreous of patients with PVR. Our results support an earlier hypothesis that a PVR-ERM, even from genomic points of view, is an aberrant form of wound healing response. Genes preferentially expressed in PVR-ERMs may play an important role in the progression of PVR and could be served as therapeutic targets.
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