Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Operating Room, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
J Proteomics. 2023 Mar 30;276:104838. doi: 10.1016/j.jprot.2023.104838. Epub 2023 Feb 9.
To investigate the changes in aqueous humor (AH) protein profiles before and after intravitreal conbercept (IVC) treatment in proliferative diabetic retinopathy (PDR) patients. Ten PDR patients provided 20 samples of AH before (pre group) and after (post group) IVC treatment. Liquid chromatography-tandem mass spectrometry was performed to identify proteins. Bioinformatics analysis was used to explore the functional relevance of differentially expressed proteins (DEPs) and hub proteins. Parallel reaction monitoring (PRM) method was used to verify the hub proteins in another 8 samples of AH before and after IVC treatment in 4 PDR patients. A total of 30 DEPs were identified, consisting of 14 downregulated proteins and 16 upregulated proteins. Bioinformatics analysis indicated that DEPs mostly involved in neutrophil degranulation, antioxidant activity, secretory granule lumen, cytoplasmic vesicle lumen, vesicle lumen, and fluid shear stress. HP, VEGFA, CTSD, and LYZ were identified as hub proteins, among which HP and CTSD were verified by PRM. In addition to decreasing the intravitreal vascular endothelial growth factor level, IVC may alter the AH protein profile in PDR patients, especially HP and CTSD, with the DEPs involved in neutrophil degranulation, antioxidant activity, secretory granule lumen, cytoplasmic vesicle lumen, vesicle lumen, and fluid shear stress. SIGNIFICANCE: Patients with proliferative diabetic retinopathy (PDR) regularly receive intravitreal conbercept treatment these days. The effect of this treatment has been determined by previous studies. However, the mechanism of IVC in PDR is not eventually determined. No studies have compared the aqueous humor (AH) protein profile before and after IVC treatment in the same patient. This is a topic deserving of further exploration. A proteomic method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilized in this study to analyze and assess the AH samples to explore the mechanism underlying the effects of IVC treatment on PDR.
为了研究增生型糖尿病视网膜病变（PDR）患者玻璃体腔内注射康柏西普（IVC）前后房水（AH）蛋白谱的变化。10 例 PDR 患者提供了 20 份 IVC 治疗前（pre 组）和治疗后（post 组）的 AH 样本。采用液相色谱-串联质谱法（LC-MS/MS）鉴定蛋白质。采用生物信息学分析探讨差异表达蛋白（DEPs）和关键蛋白的功能相关性。在 4 例 PDR 患者的 8 份 IVC 治疗前后的 AH 样本中，采用平行反应监测（PRM）方法验证关键蛋白。共鉴定出 30 个 DEPs，包括 14 个下调蛋白和 16 个上调蛋白。生物信息学分析表明，DEPs 主要涉及中性粒细胞脱颗粒、抗氧化活性、分泌颗粒腔、细胞质小泡腔、小泡腔和流体剪切力。HP、VEGFA、CTSD 和 LYZ 被鉴定为关键蛋白，其中 HP 和 CTSD 通过 PRM 得到验证。除了降低眼内血管内皮生长因子水平外，IVC 可能改变 PDR 患者的 AH 蛋白谱，特别是 HP 和 CTSD，DEPs 涉及中性粒细胞脱颗粒、抗氧化活性、分泌颗粒腔、细胞质小泡腔、小泡腔和流体剪切力。意义：目前，增生型糖尿病视网膜病变（PDR）患者经常接受玻璃体腔内注射康柏西普（IVC）治疗。这种治疗的效果已被之前的研究确定。然而，IVC 在 PDR 中的作用尚未最终确定。没有研究比较过同一患者 IVC 治疗前后的房水（AH）蛋白谱。这是一个值得进一步探索的课题。本研究采用基于液相色谱-串联质谱（LC-MS/MS）的蛋白质组学方法分析和评估 AH 样本，以探讨 IVC 治疗对 PDR 影响的作用机制。
