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首页> 外文期刊>Journal of Clinical Bioinformatics >In silico analysis of the molecular machinery underlying aqueous humor production: potential implications for glaucoma
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In silico analysis of the molecular machinery underlying aqueous humor production: potential implications for glaucoma

机译：对房水产生的分子机制进行计算机分析：对青光眼的潜在影响

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Background The ciliary body epithelia (CBE) of the eye produce the aqueous humor (AH). The equilibrium between the AH production by the CBE and the outflow through the trabecular meshwork ultimately determines the intraocular pressure (IOP). An increased IOP is a major risk factor for primary open angle glaucoma (POAG). This study aims to elucidate the molecular machinery of the most important function of the CBE: the AH production and composition, and aims to find possible new molecular clues for POAG and AH production-lowering drugs. Methods We performed a gene expression analysis of the non-pigmented (NPE) and pigmented epithelia (PE) of the human CBE of post mortem eyes. We used 44 k Agilent microarrays against a common reference design. Functional annotations were performed with the Ingenuity knowledge database. Results We built a molecular model of AH production by combining previously published physiological data with our current genomic expression data. Next, we investigated molecular CBE transport features which might influence AH composition. These features included caveolin- and clathrin vesicle-mediated transport of large biomolecules, as well as a range of substrate specific transporters. The presence of these transporters implies that, for example, immunoglobins, thyroid hormone, prostaglandins, cholesterol and vitamins can be secreted by the CBE along with the AH. In silico, we predicted some of the molecular apical interactions between the NPE and PE, the side where the two folded epithelia face each other. Finally, we found high expression of seven POAG disease genes in the plasma membrane of extracellular space of the CBE, namely APOE, CAV1, COL8A2, EDNRA, FBN1, RFTN1 and TLR4 and we found possible new targets for AH lowering drugs in the AH. Conclusions The CBE expresses many transporters, which account for AH production and/or composition. Some of these entries have also been associated with POAG. We hypothesize that the CBE may play a more prominent role than currently thought in the pathogenesis of POAG, for example by changing the composition of AH.
机译：背景技术眼睛的睫状体上皮细胞（CBE）产生房水（AH）。 CBE的AH产生与通过小梁网的流出之间的平衡最终决定了眼内压（IOP）。眼压升高是原发性开角型青光眼（POAG）的主要危险因素。这项研究旨在阐明CBE最重要功能的分子机制：AH的产生和组成，并旨在寻找可能降低POAG和AH产量的药物的新分子线索。方法我们对人死后眼睛CBE的无色素（NPE）和色素上皮细胞（PE）进行了基因表达分析。我们针对共同的参考设计使用了44 k安捷伦微阵列。功能注释是通过Ingenuity知识数据库执行的。结果我们通过将先前发表的生理数据与我们当前的基因组表达数据相结合，建立了AH生产的分子模型。接下来，我们研究了可能影响AH组成的分子CBE转运特征。这些特征包括大分子生物的小窝蛋白和网格蛋白囊泡介导的转运，以及一系列底物特异性转运蛋白。这些转运蛋白的存在意味着，例如，CBE和AH可以分泌免疫球蛋白，甲状腺激素，前列腺素，胆固醇和维生素。在计算机上，我们预测了NPE和PE（两个折叠的上皮彼此面对的一面）之间的一些分子顶端相互作用。最后，我们在CBE细胞外空间的质膜中发现了7个POAG疾病基因的高表达，即APOE，CAV1，COL8A2，EDNRA，FBN1，RFTN1和TLR4，我们发现了AH降低AH中药物的新靶标。结论CBE表达了许多转运蛋白，这些转运蛋白解释了AH的产生和/或组成。其中一些条目也与POAG相关联。我们假设CBE在POAG的发病机理中可能比目前认为的发挥更大的作用，例如通过改变AH的组成。

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