Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States of America.
McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States of America.
PLoS One. 2024 Feb 26;19(2):e0297135. doi: 10.1371/journal.pone.0297135. eCollection 2024.
Age-related macular degeneration (AMD) is a vision threatening disease in older adults. Anti-VEGF treatment is effective for the majority of neovascular AMD (nAMD) patients, although approximately 30% of nAMD patients have an incomplete response for unknown reasons. Here we assessed the contribution of single nucleotide polymorphisms (SNPs) in key angioinflammatory regulatory genes in nAMD patients with an incomplete response compared to those responsive to anti-VEGF treatment. A total of 25 responsive and 30 nAMD patients with an incomplete response to anti-vascular endothelial growth factor (anti-VEGF) treatment were examined for known SNPs that impact the structure and function of thromobospondin-1 (TSP1), Bcl-2-interacting mediator of cell death (BIM) and complement factor H (CFH). Plasma levels of C-C motif chemokine ligand 2 (CCL2/MCP1), TSP1 and VEGF were assessed by ELISA. Patients responsive to anti-VEGF treatment showed a significant increase in the TSP1 rs2228262 AA allele and a trend for the BIM (rs724710) CT allele. Consistent with previous reports, 42% of the patients responsive to anti-VEGF expressed the CC allele for CFH rs1061170. Although the CFH TT allele had similarly low prevalence in both groups, the TC allele tended to be more prevalent in patients with an incomplete response. Patients with an incomplete response also had increased plasma CCL2/MCP1 levels, consistent with the role increased inflammation has in the pathogenesis of nAMD. Our studies point to new tools to assess the potential responsiveness of nAMD patients to anti-VEGF treatment and suggest the potential use of anti-CCL2 for treatment of nAMD patients with an incomplete response to anti-VEGF.
年龄相关性黄斑变性（AMD）是一种威胁老年人视力的疾病。抗血管内皮生长因子（VEGF）治疗对大多数新生血管性 AMD（nAMD）患者有效，但大约 30%的 nAMD 患者因未知原因对治疗反应不完全。在这里，我们评估了与对抗 VEGF 治疗有反应的患者相比，反应不完全的 nAMD 患者中关键血管生成炎症调节基因的单核苷酸多态性（SNP）的贡献。共检查了 25 名对血管内皮生长因子（anti-VEGF）治疗有反应的患者和 30 名对血管内皮生长因子治疗反应不完全的 nAMD 患者，以检查影响血栓反应蛋白-1（TSP1）、Bcl-2 相互作用的细胞死亡介体（BIM）和补体因子 H（CFH）结构和功能的已知 SNP。通过 ELISA 评估 C-C 基序趋化因子配体 2（CCL2/MCP1）、TSP1 和 VEGF 的血浆水平。对血管内皮生长因子治疗有反应的患者表现出 TSP1 rs2228262 AA 等位基因的显著增加和 BIM（rs724710）CT 等位基因的趋势。与之前的报告一致，42%对血管内皮生长因子治疗有反应的患者表达了 CFH rs1061170 的 CC 等位基因。尽管 CFH TT 等位基因在两组中的患病率相似，但 TC 等位基因在反应不完全的患者中更为常见。反应不完全的患者的血浆 CCL2/MCP1 水平也升高，这与炎症增加在 nAMD 发病机制中的作用一致。我们的研究为评估 nAMD 患者对抗 VEGF 治疗的潜在反应性提供了新的工具，并表明抗 CCL2 可能用于治疗对抗 VEGF 治疗反应不完全的 nAMD 患者。
