Abstract：
Metabolic dysfunction is recognized as a contributing factor in the pathogenesis of wet age-related macular degeneration (wAMD). However, the specific metabolism-related proteins implicated in wAMD remain elusive. In this study, we assessed the expression profiles of 92 metabolism-related proteins in aqueous humor (AH) samples obtained from 44 wAMD patients and 44 cataract control patients. Our findings revealed significant alterations in the expression of 60 metabolism-related proteins between the two groups. Notably, ANGPTL7 and METRNL displayed promising diagnostic potential for wAMD, as evidenced by area under the curve values of 0.88 and 0.85, respectively. Subsequent validation studies confirmed the upregulation of ANGPTL7 and METRNL in the AH of wAMD patients and in choroidal neovascularization (CNV) models. Functional assays revealed that increased ANGPTL7 and METRNL played a pro-angiogenic role in endothelial biology by promoting endothelial cell proliferation, migration, tube formation, and spouting in vitro. Moreover, in vivo studies revealed the pro-angiogenic effects of ANGPTL7 and METRNL in CNV formation. In conclusion, our findings highlight the association between elevated ANGPTL7 and METRNL levels and wAMD, suggesting their potential as novel predictive and diagnostic biomarkers for this condition. These results underscore the significance of ANGPTL7 and METRNL in the context of wAMD pathogenesis and offer new avenues for future research and therapeutic interventions.
摘要：
代谢功能障碍被认为是湿性年龄相关性黄斑变性（wAMD）发病机理的促成因素。然而,与wAMD相关的特定代谢相关蛋白仍然难以捉摸.在这项研究中,我们评估了来自44例wAMD患者和44例白内障对照患者的房水(AH)样本中92种代谢相关蛋白的表达谱.我们的发现揭示了两组之间60种代谢相关蛋白表达的显着变化。值得注意的是,ANGPTL7和METRNL对wAMD显示出有希望的诊断潜力，曲线下面积分别为0.88和0.85。随后的验证研究证实了在wAMD患者的AH和脉络膜新生血管(CNV)模型中ANGPTL7和METRNL的上调。功能测定显示，增加的ANGPTL7和METRNL通过促进内皮细胞增殖在内皮生物学中起促血管生成作用，迁移,管形成,在体外喷出。此外，体内研究揭示了ANGPTL7和METRNL在CNV形成中的促血管生成作用。总之,我们的发现强调了升高的ANGPTL7和METRNL水平与WAMD之间的关联，表明它们作为这种情况的新型预测和诊断生物标志物的潜力。这些结果强调了ANGPTL7和METRNL在wAMD发病机制中的重要性，并为未来的研究和治疗干预提供了新的途径。
