Comparative gene expression study and pathway analysis of the human iris- and the retinal pigment epithelium.
Comparative gene expression study and pathway analysis of the human iris- and the retinal pigment epithelium.
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人虹膜和视网膜色素上皮的比较基因表达研究和途径分析。
DOI：
10.1371/journal.pone.0182983
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Bergen AA
中科院分区：
文献类型：
--
作者：
Bennis A;Ten Brink JB;Moerland PD;Heine VM;Bergen AA
视网膜色素上皮(RPE)是眼球后部的神经单层。RPE的退化会导致严重的视力丧失，这些疾病到目前为止还无法治愈，例如老年性黄斑变性和某些形式的视网膜色素变性。未来有希望的替代疗法可能是在体外将自体虹膜上皮细胞转分化为RPE，随后进行移植。在这项研究中，我们比较了虹膜上皮(IE)和RPE的基因表达谱。我们收集了5只新鲜冷冻的人供眼的RPE和IE细胞，分别用激光解剖显微镜和切割法进行了观察。我们使用44K安捷伦人类微阵列进行了全基因组表达谱分析。我们利用R和独创性知识库，在基因和功能网络水平上研究了基因表达谱。与RPE和IE相关的主要分子通路非常相似，并产生基本的神经上皮细胞功能。然而，我们也发现了主要的特异性差异：例如，与视觉周期和视黄醇生物合成相关的基因和分子通路在RPE中的表达显著高于IE。有趣的是，Wnt和芳香烃受体(AhR-)信号通路在IE中的表达比在RPE中高得多，这分别表明IE可能处于多能性和高解毒状态。这项研究对RPE和IE的表达谱之间的异同进行了评估。我们的数据结合文献的数据，代表了对转录变异的最全面的视角，这可能支持未来对IE治疗性移植发展的研究。
The retinal pigment epithelium (RPE) is a neural monolayer lining the back of the eye. Degeneration of the RPE leads to severe vision loss in, so far incurable, diseases such as age-related macular degeneration and some forms of retinitis pigmentosa. A promising future replacement therapy may be autologous iris epithelial cell transdifferentiation into RPE in vitro and, subsequently, transplantation. In this study we compared the gene expression profiles of the iris epithelium (IE) and the RPE. We collected both primary RPE- and IE cells from 5 freshly frozen human donor eyes, using respectively laser dissection microscopy and excision. We performed whole-genome expression profiling using 44k Agilent human microarrays. We investigated the gene expression profiles on both gene and functional network level, using R and the knowledge database Ingenuity. The major molecular pathways related to the RPE and IE were quite similar and yielded basic neuro-epithelial cell functions. Nonetheless, we also found major specific differences: For example, genes and molecular pathways, related to the visual cycle and retinol biosynthesis are significantly higher expressed in the RPE than in the IE. Interestingly, Wnt and aryl hydrocarbon receptor (AhR-) signaling pathways are much higher expressed in the IE than in the RPE, suggesting, respectively, a possible pluripotent and high detoxification state of the IE. This study provides a valuation of the similarities and differences between the expression profiles of the RPE and IE. Our data combined with that of the literature, represent a most comprehensive perspective on transcriptional variation, which may support future research in the development of therapeutic transplantation of IE.
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影响因子：
3.7
作者：
Janssen S;Laermans J;Iwakura H;Tack J;Depoortere I
通讯作者：
Depoortere I
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3.3
作者：
Abe, T;Tomita, H;Tamai, M
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Tamai, M
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3.7
作者：
Hagglund, Anna-Carin;Berghard, Anna;Carlsson, Leif
通讯作者：
Carlsson, Leif
影响因子：
4.8
作者：
Jasty, Srilatha;Srinivasan, Priyadharashni;Subramanian, Krishnakumar
通讯作者：
Subramanian, Krishnakumar
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作者：
Dwyer, Mary A.;Kazmin, Dmitri;Malek, Goldis
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Malek, Goldis