The keratoconus corneal proteome: loss of epithelial integrity and stromal degeneration.

The keratoconus corneal proteome: loss of epithelial integrity and stromal degeneration.
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DOI:
10.1016/j.jprot.2013.05.023
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发表时间:
2013-07-11
影响因子:
3.3
通讯作者:
Chakravarti S
Chakravarti S
中科院分区:
生物学2区
文献类型:
--
作者:
Chaerkady R;Shao H;Scott SG;Pandey A;Jun AS;Chakravarti S

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圆锥角膜是一种变薄的角膜营养不良,始于青少年早期,最终需要角膜移植来恢复视力。在这里,我们进行了高度灵敏的质谱分析上皮和基质从圆锥角膜和正常供体角膜。我们在上皮和间质的合并数据中分别鉴定了总共932和1,157种蛋白质。技术重复显示所有常见蛋白质水平的强相关性(≥ 0.88),表明数据中的技术差异非常低。对圆锥角膜角膜上皮蛋白提取物中增加最多(≥ 1.5倍)和减少最多(≤ 0.8倍)的蛋白进行分析,确定了与皮肤疾病、炎症、上皮分层和间质变化相关的蛋白。增加的蛋白质包括角蛋白6A,16和波形蛋白,而铁转运蛋白乳转铁蛋白减少。圆锥角膜基质蛋白质组提示内质网应激、氧化应激和许多细胞外基质蛋白聚糖核心蛋白、光蛋白聚糖和角膜蛋白聚糖、I型、III型、V型和XII型胶原蛋白的广泛减少。细胞凋亡和内吞相关蛋白的显著增加表明基质的常驻细胞角膜细胞发生退行性变化。这是最全面的角膜蛋白质组分析,突出了圆锥角膜与其他神经退行性疾病的相似性。
Keratoconus is a thinning corneal dystrophy that begins in the early teenage years and ultimately requires cornea transplantation to restore vision. Here we conducted a highly sensitive mass spectrometric analysis of the epithelium and the stroma from keratoconus and normal donor corneas. We identified a total of 932 and 1,157 proteins in the consolidated data of the epithelium and stroma, respectively. Technical replicates showed strong correlations (≥ 0.88) in levels of all common proteins, indicating very low technical variations in the data. Analysis of the most increased (≥ 1.5 fold) and decreased (≤ 0.8 fold) proteins in the keratoconus corneal epithelial protein extracts identified proteins related to dermal diseases, inflammation, epithelial stratification and mesenchymal changes. Increased proteins included keratins 6A, 16 and vimentin, while the iron transporter lactotransferrin was decreased. The keratoconus stromal proteome suggest endoplasmic reticular stress, oxidative stress and widespread decreases in many extracellular matrix proteoglycan core proteins, lumican and keratocan, collagen types I, III, V and XII. Marked increase in apoptosis and endocytosis-related proteins suggest degenerative changes in keratocytes, the resident cells of the stroma. This is the most comprehensive proteome analysis of the cornea that highlights similarities of keratoconus with other neurodegenerative diseases.
DOI: 10.1016/j.ophtha.2004.11.050
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