Wang Yuelin, Xing Dongjun, Duan Jialiang, Zhou Huiying, Meng Lihui, Geng Shuang, Chen Huan, Han Ruoan, Li Zhiqing, Ma Jingxue, Chen Youxin
Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences, Beijing, China.
Acta Ophthalmol. 2025 Mar;103(2):e136-e145. doi: 10.1111/aos.16768. Epub 2024 Oct 18.
Patients with polypoidal choroidal vasculopathy (PCV) exhibit variability in response to anti-VEGF therapy. This study aimed to analyse the aqueous humour proteomic profiles of PCV patients and provide preliminary insights for the identification of biomarkers associated with anti-VEGF drug responsiveness.
PCV patients who were treatment-naïve or untreated for more than 3 months were prospectively recruited from two hospitals in Beijing and Tianjin. Based on the relative changes in central macular thickness (ΔCMT/baseline-CMT) before and after anti-VEGF treatment, the PCV patients were divided into a good response (GR) group (≤-25%) and a poor response (PR) group (>-25%). Aqueous humour proteomics was performed by the Data-independent Acquisition-Mass Spectrometry (DIA-MS) method, and differentially expressed proteins (DEPs) analysis between the different PCV groups and the control group was conducted. Key DEPs were selected for preliminary validation in the aqueous humour using the Luminex method retrospectively.
A total of 31 PCV patients (31 eyes) were included, 13 in the GR group and 18 in the PR group. A total of 414 DEPs were identified, including 36 significantly upregulated proteins, such as G protein regulatory factor 10 (RGS10), podocin (PODN) and epidermal growth factor (EGF), and 32 downregulated proteins, including RAB11FIP4 (Rab11 family-interacting protein 4), α-synuclein (SNCA), haemoglobin subunit δ (HBD) and interleukin 6 (IL6). Compared to the cataract control group (10 eyes), 134 proteins were significantly upregulated, and 72 were downregulated. KEGG pathway enrichment analysis revealed that the GR and PR groups differ in terms of cell communication, and cell signal transduction. Protein-protein interaction analysis revealed interactions between EGF and various DEPs. Validation of aqueous humour proteins using the Luminex method revealed that changes in the levels of EGF were associated with the anti-VEGF treatment response in PCV patients.
PCV patients with good or poor anti-VEGF responses exhibit distinct aqueous humour proteomic profiles. Aqueous EGF may serve as a biomarker for the 'precise treatment' of PCV.
息肉状脉络膜血管病变（PCV）患者对抗VEGF治疗的反应存在差异。本研究旨在分析PCV患者房水蛋白质组学特征，为鉴定与抗VEGF药物反应性相关的生物标志物提供初步见解。
从北京和天津的两家医院前瞻性招募初治或未治疗超过3个月的PCV患者。根据抗VEGF治疗前后中心黄斑厚度的相对变化（ΔCMT/基线-CMT），将PCV患者分为良好反应（GR）组（≤-25%）和不良反应（PR）组（>-25%）。采用数据非依赖采集质谱（DIA-MS）方法进行房水蛋白质组学分析，并对不同PCV组与对照组之间的差异表达蛋白（DEP）进行分析。回顾性地选择关键DEP，使用Luminex方法在房水中进行初步验证。
共纳入31例PCV患者（31只眼），GR组13例，PR组18例。共鉴定出414个DEP，包括36个显著上调的蛋白，如G蛋白调节因子10（RGS10）、足突蛋白（PODN）和表皮生长因子（EGF），以及32个下调的蛋白，包括RAB11FIP4（Rab11家族相互作用蛋白4）、α-突触核蛋白（SNCA）、血红蛋白亚基δ（HBD）和白细胞介素6（IL6）。与白内障对照组（10只眼）相比，134个蛋白显著上调，72个蛋白下调。KEGG通路富集分析显示，GR组和PR组在细胞通讯和细胞信号转导方面存在差异。蛋白质-蛋白质相互作用分析显示EGF与各种DEP之间存在相互作用。使用Luminex方法对房水蛋白进行验证，结果显示EGF水平的变化与PCV患者的抗VEGF治疗反应相关。
抗VEGF反应良好或不良的PCV患者表现出不同的房水蛋白质组学特征。房水EGF可能作为PCV“精准治疗”的生物标志物。
