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Abstract：
UNASSIGNED: The purpose of this study was to investigate the molecular mechanisms underlying anti-vascular endothelial growth factor (anti-VEGF) efficacy and response variability in neovascular age-related macular degeneration (nAMD) using longitudinal proteomic and metabolomic analysis alongside three-dimensional lesion measurements.
UNASSIGNED: In this prospective study, 54 treatment-naive patients with nAMD underwent \"3+ pro re nata\" (3+PRN) anti-VEGF regimens followed for at least 12 weeks. Aqueous humors were collected pre- and post-treatment for proteomic and metabolomic analysis. Three-dimensional optical coherence tomography (OCT) and OCT angiography assessed different types of nAMD lesion volumes and areas.
UNASSIGNED: There were 1350 proteins and 1268 metabolites that were identified in aqueous humors, with 301 proteins and 353 metabolites significantly altered during anti-VEGF treatment, enriched in pathways of angiogenesis, energy metabolism, signal transduction, and neurofunctional regulation. Sixty-seven changes of (Δ) molecules significantly correlated with at least one type of ΔnAMD lesion. Notably, proteins FGA, TALDO1, and ASPH significantly decreased during treatment, with their reductions correlating with greater lesion regression in at least two lesion types. Conversely, despite that YIPF3 also showed significant downregulation, its decrease was associated with poorer regression in total nAMD lesion and subretinal hyper-reflective material.
UNASSIGNED: This study identifies FGA, TALDO1, and ASPH as potential key molecules in the efficacy of anti-VEGF therapy, whereas YIPF3 may be a key factor in poor response. The integration of longitudinal three-dimensional lesion analysis with multi-omics provides valuable insights into the mechanisms and response variability of anti-VEGF treatment in nAMD.
UNASSIGNED: In this prospective study, 54 treatment-naive patients with nAMD underwent \"3+ pro re nata\" (3+PRN) anti-VEGF regimens followed for at least 12 weeks. Aqueous humors were collected pre- and post-treatment for proteomic and metabolomic analysis. Three-dimensional optical coherence tomography (OCT) and OCT angiography assessed different types of nAMD lesion volumes and areas.
UNASSIGNED: There were 1350 proteins and 1268 metabolites that were identified in aqueous humors, with 301 proteins and 353 metabolites significantly altered during anti-VEGF treatment, enriched in pathways of angiogenesis, energy metabolism, signal transduction, and neurofunctional regulation. Sixty-seven changes of (Δ) molecules significantly correlated with at least one type of ΔnAMD lesion. Notably, proteins FGA, TALDO1, and ASPH significantly decreased during treatment, with their reductions correlating with greater lesion regression in at least two lesion types. Conversely, despite that YIPF3 also showed significant downregulation, its decrease was associated with poorer regression in total nAMD lesion and subretinal hyper-reflective material.
UNASSIGNED: This study identifies FGA, TALDO1, and ASPH as potential key molecules in the efficacy of anti-VEGF therapy, whereas YIPF3 may be a key factor in poor response. The integration of longitudinal three-dimensional lesion analysis with multi-omics provides valuable insights into the mechanisms and response variability of anti-VEGF treatment in nAMD.
摘要：
这项研究的目的是使用纵向蛋白质组学和代谢组学分析以及三维病变测量来研究新生血管性年龄相关性黄斑变性（nAMD）中抗血管内皮生长因子（抗VEGF）功效和反应变异性的分子机制。
■在这项前瞻性研究中，54例未接受治疗的nAMD患者接受了“3+prorenata”（3+PRN）抗VEGF方案至少12周。收集治疗前和治疗后的房水，用于蛋白质组学和代谢组学分析。三维光学相干断层扫描（OCT）和OCT血管造影评估了不同类型的nAMD病变体积和面积。
■在房水中鉴定出1350种蛋白质和1268种代谢物，在抗VEGF治疗期间，301种蛋白质和353种代谢物发生了显著改变，富含血管生成途径，能量代谢，信号转导，和神经功能调节。（Δ）分子的67个变化与至少一种ΔnAMD病变显着相关。值得注意的是,蛋白质FGA,治疗期间TALDO1和ASPH显著下降，它们的减少与至少两种病变类型的病变消退更大相关。相反，尽管YIPF3也显示出显着的下调，其减少与总nAMD病变和视网膜下高反射物质的消退较差相关.
■这项研究确定了FGA，TALDO1和ASPH作为抗VEGF治疗疗效的潜在关键分子，而YIPF3可能是反应不佳的关键因素。纵向三维病变分析与多组学的整合为nAMD中抗VEGF治疗的机制和反应变异性提供了有价值的见解。
■在这项前瞻性研究中，54例未接受治疗的nAMD患者接受了“3+prorenata”（3+PRN）抗VEGF方案至少12周。收集治疗前和治疗后的房水，用于蛋白质组学和代谢组学分析。三维光学相干断层扫描（OCT）和OCT血管造影评估了不同类型的nAMD病变体积和面积。
■在房水中鉴定出1350种蛋白质和1268种代谢物，在抗VEGF治疗期间，301种蛋白质和353种代谢物发生了显著改变，富含血管生成途径，能量代谢，信号转导，和神经功能调节。（Δ）分子的67个变化与至少一种ΔnAMD病变显着相关。值得注意的是,蛋白质FGA,治疗期间TALDO1和ASPH显著下降，它们的减少与至少两种病变类型的病变消退更大相关。相反，尽管YIPF3也显示出显着的下调，其减少与总nAMD病变和视网膜下高反射物质的消退较差相关.
■这项研究确定了FGA，TALDO1和ASPH作为抗VEGF治疗疗效的潜在关键分子，而YIPF3可能是反应不佳的关键因素。纵向三维病变分析与多组学的整合为nAMD中抗VEGF治疗的机制和反应变异性提供了有价值的见解。
