Lynch Anne M, Wagner Brandie D, Weiss Sophie J, Wall Kirsten M, Palestine Alan G, Mathias Marc T, Siringo Frank S, Cathcart Jennifer N, Patnaik Jennifer L, Drolet Daniel W, Janjic Nebojsa, Mandava Naresh
Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA.
Transl Vis Sci Technol. 2019 Jan 25;8(1):14. doi: 10.1167/tvst.8.1.14. eCollection 2019 Jan.
To explore top-ranked plasma proteins related to neovascular age-related macular degeneration (AMD) and geographic atrophy (GA), and explore pathways related to neovascular AMD and GA.
We conducted a pilot study of patients with neovascular AMD ( = 10), GA ( = 10), and age-matched cataract controls ( = 10) who were recruited into an AMD registry. We measured 4001 proteins in ethylenediaminetetraacetic acid plasma samples using an aptamer-based proteomic technology. Relative concentrations of each of 4001 proteins were log (base 2) transformed and compared between cases of neovascular AMD and GA versus controls using linear regression. Pathway analysis was conducted using pathways downloaded from Reactome.
In this pilot study higher levels of vinculin and lower levels of CD177 were found in patients with neovascular AMD compared with controls. Neuregulin-4 was higher and soluble intercellular adhesion molecule-1 was lower in patients with GA compared with controls. For neovascular AMD, cargo trafficking to the periciliary membrane, fibroblast growth factor receptor 3b ligand binding and activation, and vascular endothelial growth factor-related pathways were in the top ranked pathways. The top-ranked pathways for GA included several related to ErbB4 signaling.
We found different proteins and different pathways associated with neovascular AMD and GA. Vinculin and some of the top-ranked pathways have been previously associated with AMD, whereas others have not been described.
Biomarkers identified in plasma likely reflect systemic alterations in protein expression and may improve our understanding of the mechanisms leading to AMD.
探索与新生血管性年龄相关性黄斑变性（AMD）和地图样萎缩（GA）相关的排名靠前的血浆蛋白，并探索与新生血管性AMD和GA相关的通路。
我们对纳入AMD登记处的新生血管性AMD患者（n = 10）、GA患者（n = 10）和年龄匹配的白内障对照者（n = 10）进行了一项初步研究。我们使用基于适配体的蛋白质组学技术在乙二胺四乙酸血浆样本中测量了4001种蛋白质。对4001种蛋白质中的每一种的相对浓度进行以2为底的对数转换，并使用线性回归比较新生血管性AMD和GA病例与对照之间的差异。使用从Reactome下载的通路进行通路分析。
在这项初步研究中，与对照相比，新生血管性AMD患者中发现纽蛋白水平较高，而CD177水平较低。与对照相比，GA患者中神经调节蛋白-4水平较高，可溶性细胞间黏附分子-1水平较低。对于新生血管性AMD，向睫周膜的货物运输、成纤维细胞生长因子受体3b配体结合和激活以及血管内皮生长因子相关通路在排名靠前的通路中。GA排名靠前的通路包括几个与ErbB4信号传导相关的通路。
我们发现了与新生血管性AMD和GA相关的不同蛋白质和不同通路。纽蛋白和一些排名靠前的通路以前与AMD相关，而其他一些则未被描述。
血浆中鉴定出的生物标志物可能反映蛋白质表达的全身改变，并可能改善我们对导致AMD的机制的理解。
