Effect of ranibizumab on diabetic retinopathy via the vascular endothelial growth factor/STAT3/glial fibrillary acidic protein pathway  

作　　者：Ye-Ting Lin Jian Tan Yu-Lin Tao Wei-Wen Hu Yi-Cang Wang Jing Huang Qiong Zhou Ang Xiao 

机构地区：[1]Department of Ophthalmology,The First Affiliated Hospital of Nanchang University,Jiangxi Medical College,Nanchang University,Nanchang 330006,Jiangxi Province,China [2]Department of Ophthalmology,The Affiliated Hospital of Jiangxi University of Chinese Medicine,Nanchang 330006,Jiangxi Province,China

出　　处：《World Journal of Diabetes》2025年第5期234-253,共20页世界糖尿病杂志(英文)

基　　金：Supported by the Natural Science Foundation of Jiangxi Province,No.20242BAB25489;National Natural Science Foundation of China,No.82260211 and No.81460092;Key Research and Development Project in Jiangxi Province,No.20203BBG73058;Chinese Medicine Science and Technology Project in Jiangxi Province,No.2020A0166。

摘　　要：BACKGROUND Diabetic retinopathy(DR)is the leading cause of vision loss in patients with diabetes.The vascular endothelial growth factor(VEGF)pathway plays a critical role in the pathogenesis of DR,and ranibizumab,an anti-VEGF agent,has shown promise in its treatment.Signal transducer and activator of transcription 3(STAT3)is involved in inflammatory processes and cellular signaling,while glial fibrillary acidic protein(GFAP)is a marker of glial cell activation,both contributing to retinal damage in DR.However,the mechanisms by which ranibizumab affect early-stage DR through the VEGF/STAT3/GFAP pathway are not fully understood.AIM To investigate the role of ranibizumab in early DR via the VEGF/STAT3/GFAP pathway.METHODS Adult retinal pigment epithelial 19(ARPE-19)cells and human retinal microvascular endothelial cells(HRMECs)were cultured under high-glucose conditions to simulate a diabetic environment.The effects of ranibizumab on cytokine mRNA and protein expression were analyzed by quantitative polymerase chain reaction and Western blot analysis.A diabetic rat model was induced with streptozotocin(60 mg/kg).Retinal changes,including retinal ganglion cell(RGC)apoptosis,vascular alterations,and cytokine expression,were evaluated using fundus fluorescein angiography,hematoxylin and eosin and periodic acid Schiff staining,immunofluorescence,confocal imaging,and Western blot analysis.RESULTS High-glucose conditions significantly increased the mRNA and protein levels of VEGF,STAT3,GFAP,and other cytokines in ARPE-19 and HRMECs.However,these levels were partially suppressed by ranibizumab.RGC apoptosis,vascular leakage,and elevated cytokine expression were observed during early-stage DR in diabetic rats.Ranibizumab treatment in diabetic rats reduced cytokine expression,restored RGCs,and repaired vascular networks.CONCLUSION Intravitreal ranibizumab modulates the VEGF/STAT3/GFAP pathway,suppresses cytokine expression,and promotes retinal repair,effectively delaying or preventing early DR progression.

关 键 词：Diabetic retinopathy RANIBIZUMAB Early stage Vascular endothelial growth factor Signal transducer and activator of transcription 3 Glial fibrillary acidic protein 

分 类 号：R73[医药卫生—肿瘤]