抗肿瘤坏死因子- α重组腺相关病毒在实验性自身免疫性葡萄膜炎模型中的作用

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research Pub Date : 2025-02-06 DOI:10.1016/j.exer.2025.110273

Baiyi Li , Chuan Zhao , Shengjie Guo , Xueru Li , Hui Zhang , Yanan Duan , Mi Zhang , Qingqin Tao , Peiran Zhou , Xiaorong Li , Xiaomin Zhang

{"title":"抗肿瘤坏死因子- α重组腺相关病毒在实验性自身免疫性葡萄膜炎模型中的作用","authors":"Baiyi Li , Chuan Zhao , Shengjie Guo , Xueru Li , Hui Zhang , Yanan Duan , Mi Zhang , Qingqin Tao , Peiran Zhou , Xiaorong Li , Xiaomin Zhang","doi":"10.1016/j.exer.2025.110273","DOIUrl":null,"url":null,"abstract":"<div><div>Uveitis treatment is associated with side effects and inconsistent outcomes. Existing treatments often fail to provide targeted and sustained relief; thus, novel therapeutic approaches are needed. Among these, gene therapy using adeno-associated virus (AAV) vectors target specific retinal cells, show low immunogenicity, and demonstrate sustained gene expression, making it a potential advancement in uveitis treatment. Therefore, we utilized a AAV2 system encapsulating encoded anti-tumor necrosis factor-alpha (TNF-α) antibody to assess its efficacy in the treatment of experimental autoimmune uveitis (EAU) in mice. Compared with the AAV2-GFP group, AAV2-ADA-injected mice showed significantly reduced clinical, OCT, and histopathological scores in EAU with lower percentages of Th1 and Th17 cells in the eyes and higher percentages of Treg cells in the draining lymph nodes (LN). This study demonstrated the safety and effects of AAV2-ADA in EAU treatment, providing a promising therapeutic strategy for uveitis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"253 ","pages":"Article 110273"},"PeriodicalIF":3.0000,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Recombinant adeno-associated virus with anti-tumor necrosis factor-alpha in an experimental autoimmune uveitis model\",\"authors\":\"Baiyi Li , Chuan Zhao , Shengjie Guo , Xueru Li , Hui Zhang , Yanan Duan , Mi Zhang , Qingqin Tao , Peiran Zhou , Xiaorong Li , Xiaomin Zhang\",\"doi\":\"10.1016/j.exer.2025.110273\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Uveitis treatment is associated with side effects and inconsistent outcomes. Existing treatments often fail to provide targeted and sustained relief; thus, novel therapeutic approaches are needed. Among these, gene therapy using adeno-associated virus (AAV) vectors target specific retinal cells, show low immunogenicity, and demonstrate sustained gene expression, making it a potential advancement in uveitis treatment. Therefore, we utilized a AAV2 system encapsulating encoded anti-tumor necrosis factor-alpha (TNF-α) antibody to assess its efficacy in the treatment of experimental autoimmune uveitis (EAU) in mice. Compared with the AAV2-GFP group, AAV2-ADA-injected mice showed significantly reduced clinical, OCT, and histopathological scores in EAU with lower percentages of Th1 and Th17 cells in the eyes and higher percentages of Treg cells in the draining lymph nodes (LN). This study demonstrated the safety and effects of AAV2-ADA in EAU treatment, providing a promising therapeutic strategy for uveitis.</div></div>\",\"PeriodicalId\":12177,\"journal\":{\"name\":\"Experimental eye research\",\"volume\":\"253 \",\"pages\":\"Article 110273\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-02-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental eye research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014483525000442\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental eye research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014483525000442","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

葡萄膜炎的治疗与副作用和不一致的结果有关。现有的治疗方法往往不能提供有针对性和持续的缓解；因此，需要新的治疗方法。其中，利用腺相关病毒（adeno-associated virus， AAV）载体的基因治疗靶向特异性视网膜细胞，具有低免疫原性，且具有持续的基因表达，使其成为治疗葡萄膜炎的潜在进展。因此，我们利用AAV2系统封装编码抗肿瘤坏死因子-α (TNF-α)抗体来评估其对小鼠实验性自身免疫性葡萄膜炎（EAU）的治疗效果。与AAV2-GFP组相比，注射aav2 - ada的小鼠在EAU中的临床、OCT和组织病理学评分显著降低，眼睛中Th1和Th17细胞的百分比较低，引流淋巴结（LN）中Treg细胞的百分比较高。本研究证实了AAV2-ADA在EAU治疗中的安全性和有效性，为葡萄膜炎提供了一种有前景的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Recombinant adeno-associated virus with anti-tumor necrosis factor-alpha in an experimental autoimmune uveitis model

Uveitis treatment is associated with side effects and inconsistent outcomes. Existing treatments often fail to provide targeted and sustained relief; thus, novel therapeutic approaches are needed. Among these, gene therapy using adeno-associated virus (AAV) vectors target specific retinal cells, show low immunogenicity, and demonstrate sustained gene expression, making it a potential advancement in uveitis treatment. Therefore, we utilized a AAV2 system encapsulating encoded anti-tumor necrosis factor-alpha (TNF-α) antibody to assess its efficacy in the treatment of experimental autoimmune uveitis (EAU) in mice. Compared with the AAV2-GFP group, AAV2-ADA-injected mice showed significantly reduced clinical, OCT, and histopathological scores in EAU with lower percentages of Th1 and Th17 cells in the eyes and higher percentages of Treg cells in the draining lymph nodes (LN). This study demonstrated the safety and effects of AAV2-ADA in EAU treatment, providing a promising therapeutic strategy for uveitis.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Experimental eye research 医学-眼科学

CiteScore

6.80

自引率

5.90%

发文量

323

审稿时长

66 days

期刊介绍： The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.