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作 者:Ting-Ting Feng Xiang Gao An-Ran Liang Bo-Wen Zhao Guang-Hui He Song Chen
机构地区:[1]Clinical College of Ophthalmology,Tianjin Medical University,Tianjin 300070,China [2]Tianjin Key Laboratory of Ophthalmology and Visual Science,Tianjin Eye Institute,Tianjin Eye Hospital,Tianjin 300020,China [3]Key Laboratory of Ophthalmology,Anyang Eye Hospital,Anyang 455000,Henan Province,China [4]Department of Ophthalmology,Jining No.1 People’s Hospital,Jining 272011,Shandong Province,China
出 处:《International Journal of Ophthalmology(English edition)》2024年第4期676-685,共10页国际眼科杂志(英文版)
基 金:Supported by Tianjin Key Medical Discipline Specialty Construction Project(No.TJYXZDXK-016A);Henan Provincial Department of Science and Technology(No.LHGJ20200802).
摘 要:AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of PDR.METHODS:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free technology.Statistically differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were analyzed.RESULTS:A total of 12 samples were analyzed.The proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were down-regulated.We found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept treatment.GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR.In addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural regulation.In addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in PDR.CONCLUSION:Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR.Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.
关 键 词:VITREOUS proliferative diabetic retinopathy PROTEOME 4D label-free
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