中国临床药学杂志2026，Vol.35Issue(2)：113-120,8.DOI:10.19577/j.1007-4406.2026.02.003
预防湿性老年性黄斑变性的潜在药物靶点研究
Research on potential drug targets for wet senile macular degeneration
孙红 1闫晶超 1辛秀 1黄滔敏1
作者信息
- 1. 复旦大学附属眼耳鼻喉科医院药剂科,上海 200031
- 折叠
摘要
Abstract
AIM To identify potential drug targets for preventing wet senile macular degeneration(wet-SMD).METHODS A multi-level transcriptome-wide association study(TWAS)was performed to assess the effect of gene expression at the blood,brain and single-cell levels on the risk of wet-SMD.The overlap genes were further validated by Multimarker Analysis of Genomic Annotation(MAGMA)and strengthened by colocalization analyses.Protein-protein interaction network,enrichment,cell-cell communication,drug screening and molecular docking analysis were conducted to investigate the functional roles of candidate targets and potential drugs for preventing wet-SMD.RESULTS PLEKHA1 and RAPGEF6 were identified by multi-level TWAS,confirmed by MAGMA and strengthened by colocalization analysis.Cell-cell communication analysis indicated that signaling through TGFB1-(ACVR1B+TGFBR2),ANGPTL4-CDH5,MDK-NCL and VEGFB-VEGFR1 pathways may be implicated in the mechanism of PLEKHA1 on wet-SMD.VEGFB-VEGFR1 and MDK-SDC4 interactions could be key to understanding the role of RAPGEF6 in wet-SMD pathology.Drug screening and molecular docking analysis suggested that α-tocopherol and citric acid might be the potential drugs for preventing wet-SMD.CONCLUSION PLEKHA1 and RAPGEF6 are associated with wet-SMD risk,which might enhance our understanding of wet-SMD pathogenesis and highlight potential drug targets for prevention of wet-SMD.关键词
转录组关联研究/易感基因/药物靶点/湿性老年性黄斑变性Key words
transcriptome-wide association study/susceptibility gene/drug target/wet senile macular degeneration分类
医药卫生引用本文复制引用
孙红,闫晶超,辛秀,黄滔敏..预防湿性老年性黄斑变性的潜在药物靶点研究[J].中国临床药学杂志,2026,35(2):113-120,8.
