Glaucoma related Proteomic Alterations in Human Retina Samples.
Glaucoma related Proteomic Alterations in Human Retina Samples.
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DOI：
10.1038/srep29759
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发表时间：
2016-07-18
影响因子：
4.6
通讯作者：
Grus FH
中科院分区：
文献类型：
--
作者：
Funke S;Perumal N;Beck S;Gabel-Scheurich S;Schmelter C;Teister J;Gerbig C;Gramlich OW;Pfeiffer N;Grus FH
青光眼相关的蛋白质组学变化已在细胞和动物模型中得到证实。然而，对人类视网膜样本的蛋白质组学研究仍然很少。在目前的工作中，青光眼和非青光眼对照供体的视网膜样品已经通过最先进的质谱（MS）工作流程进行了检查，以揭示青光眼相关的蛋白质组学变化。在人视网膜样品中可以以高置信度（FDR < 1%）鉴定超过600种蛋白质。在10%的线粒体和细胞核蛋白质中观察到了明显的蛋白质组学变化。许多蛋白质显示出显著的青光眼相关水平变化（p < 0.05）或明显的改变趋势（p < 0.1）。候选人被记录为参与细胞发育，压力和细胞死亡。MS可记录应激相关蛋白的增加和新的青光眼相关候选物ADP/ATP移位酶3（ANT 3）、PC 4和SRFS 1相互作用蛋白1（DFS 70）和甲基-CpG结合蛋白2（MeCp 2）的减少。候选物可通过精确包合物质量筛选（AIMS）和免疫染色进行验证，并支持视网膜神经节细胞层（GCL）通过激光捕获显微切割（LCM）在猪和人眼冷冻切片。该工作流程允许详细查看人类视网膜蛋白质组，突出显示与青光眼相关的新分子参与者ANT 3，DFS 70和MeCp 2。
Glaucoma related proteomic changes have been documented in cell and animal models. However, proteomic studies investigating on human retina samples are still rare. In the present work, retina samples of glaucoma and non-glaucoma control donors have been examined by a state-of-the-art mass spectrometry (MS) workflow to uncover glaucoma related proteomic changes. More than 600 proteins could be identified with high confidence (FDR < 1%) in human retina samples. Distinct proteomic changes have been observed in 10% of proteins encircling mitochondrial and nucleus species. Numerous proteins showed a significant glaucoma related level change (p < 0.05) or distinct tendency of alteration (p < 0.1). Candidates were documented to be involved in cellular development, stress and cell death. Increase of stress related proteins and decrease of new glaucoma related candidates, ADP/ATP translocase 3 (ANT3), PC4 and SRFS1-interacting protein 1 (DFS70) and methyl-CpG-binding protein 2 (MeCp2) could be documented by MS. Moreover, candidates could be validated by Accurate Inclusion Mass Screening (AIMS) and immunostaining and supported for the retinal ganglion cell layer (GCL) by laser capture microdissection (LCM) in porcine and human eye cryosections. The workflow allowed a detailed view into the human retina proteome highlighting new molecular players ANT3, DFS70 and MeCp2 associated to glaucoma.