Proteomic profiles in the aqueous following anti-vegf therapy in treatment naïve neovascular age-related macular degeneration.

IF 3.3 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS
Anne M Lynch, Daniel W Drolet, Kinsey M Trinder, Shashi Gupta, Matthew J Westacott, Nebojsa Janjic, Alan G Palestine, Jennifer L Patnaik, Marc T Mathias, Naresh Mandava, Brandie D Wagner
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引用次数: 0

Abstract

Background/study objectives: Age-related macular degeneration (AMD), a degenerative disease of the photoreceptor support system of the macula, is a leading cause of vision loss in individuals over 60 years of age. In this exploratory longitudinal study, we studied VEGF-related proteins and other protein concentrations in the aqueous humor of patients with treatment naïve neovascular AMD (defined as patients with a previously untreated and recently diagnosed advanced neovascular form of AMD (NVAMD) who were eligible for an intra-vitreal administration of an anti-VEGF agent to treat choroidal neovascularization). The objectives of this small pilot study were: (1) To determine levels of VEGF-related proteins in the aqueous humor of treatment naïve NVAMD patients compared with control patients, (2) To determine whether levels of VEGF-related proteins change over time with anti-VEGF injections in NVAMD patients, (3) To put these differences into perspective relative to all protein targets and identify other off-target (non-VEGF) proteins that may be related to NVAMD or NVAMD treatment.

Methods: We used an aptamer-based proteomic technology to study protein concentrations. Cases had a sample of aqueous collected immediately prior to starting the anti-VEGF intra-vitreal injection and at two follow-up visits. Controls were cataract patients with no AMD. Aqueous was collected at the time of cataract surgery.

Results: Comparison between 9 cases and 11 controls revealed 56 proteins, out of 3,803 targets, with significant differences in baseline levels. After treatment, a decline in aqueous VEGF concentrations was indicated from two aptamer reagents, while a third recorded a significant increase. Interference studies demonstrated that the increase in levels observed for the latter reagent was due to measuring both drug-bound and free VEGF concentrations (total VEGF) while the others measured only free VEGF.

Conclusions: In this exploratory study, 56 proteins were identified that could potentially be linked with NVAMD. In interference studies free aqueous VEGF levels declined while total VEGF levels increased following anti-VEGF treatment. No large off-target effects on the proteome were observed with treatment. We illustrate how the protein interactome can mask or potentially unmask binding epitopes leading to signal changes not necessarily related to the absolute protein level.

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抗vegf治疗naïve新生血管性年龄相关性黄斑变性后水中蛋白质组学特征。
背景/研究目的:老年性黄斑变性(AMD)是黄斑光感受器支持系统的退行性疾病,是60岁以上人群视力丧失的主要原因。在这项探索性纵向研究中,我们研究了naïve新生血管性AMD治疗患者房水中vegf相关蛋白和其他蛋白浓度(定义为先前未治疗且最近诊断为晚期新生血管性AMD (NVAMD)的患者,符合玻璃体内给药抗vegf药物治疗脉络膜新生血管的条件)。这项小型试点研究的目的是:(1)确定治疗naïve NVAMD患者与对照组患者房水中vegf相关蛋白的水平,(2)确定NVAMD患者注射抗vegf后vegf相关蛋白水平是否随时间变化,(3)将这些差异与所有蛋白靶点相比较,并确定可能与NVAMD或NVAMD治疗相关的其他脱靶(非vegf)蛋白。方法:采用适体蛋白质组学技术研究蛋白质浓度。病例在开始抗vegf玻璃体注射前和两次随访时立即收集水样。对照组为无黄斑变性的白内障患者。白内障手术时收集水。结果:9例患者与11例对照组的比较显示,在3,803个靶点中,有56个蛋白的基线水平存在显著差异。治疗后,两种适体试剂显示VEGF水溶液浓度下降,而第三种适体试剂则显著增加。干扰研究表明,后一种试剂中观察到的水平增加是由于同时测量了药物结合和游离VEGF浓度(总VEGF),而其他试剂只测量了游离VEGF。结论:在这项探索性研究中,鉴定出56种可能与NVAMD相关的蛋白。在干扰研究中,在抗VEGF治疗后,游离血管内皮生长因子水平下降,而总血管内皮生长因子水平上升。治疗未观察到对蛋白质组的大脱靶效应。我们说明了蛋白质相互作用组如何掩盖或潜在地揭开结合表位,导致不一定与绝对蛋白质水平相关的信号变化。
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来源期刊
Clinical proteomics
Clinical proteomics BIOCHEMICAL RESEARCH METHODS-
CiteScore
5.80
自引率
2.60%
发文量
37
审稿时长
17 weeks
期刊介绍: Clinical Proteomics encompasses all aspects of translational proteomics. Special emphasis will be placed on the application of proteomic technology to all aspects of clinical research and molecular medicine. The journal is committed to rapid scientific review and timely publication of submitted manuscripts.
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