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首页> 外文期刊>PLoS One >Comparative gene expression study and pathway analysis of the human iris- and the retinal pigment epithelium
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Comparative gene expression study and pathway analysis of the human iris- and the retinal pigment epithelium

机译：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

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Background 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. Methods 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. Results 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. Conclusions 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.
机译：背景技术视网膜色素上皮（RPE）是位于眼后的神经单层。 RPE的变性导致迄今为止无法治愈的疾病中严重的视力丧失，例如与年龄有关的黄斑变性和某些形式的色素性视网膜炎。未来有希望的替代疗法可能是自体虹膜上皮细胞体外分化为RPE，然后进行移植。在这项研究中，我们比较了虹膜上皮（IE）和RPE的基因表达谱。方法我们分别使用激光解剖显微镜和切除术从5只新鲜冷冻的人类供体眼中收集了RPE和IE原代细胞。我们使用44k Agilent人类微阵列进行了全基因组表达谱分析。我们使用R和知识数据库Ingenuity在基因和功能网络水平上研究了基因表达谱。结果与RPE和IE相关的主要分子途径非常相似，并产生了基本的神经上皮细胞功能。尽管如此，我们还发现了主要的特定差异：例如，与视觉周期和视黄醇生物合成相关的基因和分子途径在RPE中的表达明显高于IE。有趣的是，Wnt和芳烃受体（AhR-）信号通路在IE中的表达要比RPE高得多，分别表明IE可能处于多能和高解毒状态。结论本研究评估了RPE和IE的表达谱之间的异同。我们的数据与文献数据相结合，代表了关于转录变异的最全面的观点，这可能支持IE治疗性移植发展的未来研究。

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