摘要
新生血管性年龄相关性黄斑变性(nAMD)是老年人群主要的致盲眼病之一,早发现、早治疗尤为重要。目前,nAMD的治疗主要为抗血管内皮生长因子(VEGF)和激光治疗等对症疗法,这并不能解决nAMD持续性活动的问题,反复治疗增加患者的经济负担,也增加了眼压升高、炎症反应等并发症的发生。近年来,基因疗法的广泛应用为nAMD的治疗带来了更多可能。它以病毒为载体,将目的基因cDNA与载体组合,利用病毒感染宿主细胞的特点,实现了目的基因在宿主细胞内的表达。在动物实验成功的基础上,国内外学者相继开展Ⅰ期、Ⅱ期临床试验,其靶点有色素上皮衍生因子、RNA干扰、可溶性VEGF受体-1、内皮抑素和血管抑素、抗人VEGF抗体片段、可溶性CD59、阿柏西普、补体因子Ⅰ等,取得了一定的成效,但也暴露出一些问题。本文就基因疗法治疗nAMD的机制、临床试验研究进展及存在的问题进行综述,并提出未来基因疗法的前景展望。
Neovascular macular degeneration(nAMD)is one of the main eye diseases causing blindness in the elderly population.Early detection and early treatment are particularly important.At present,the treatment of nAMD is mainly symptomatic,including anti-vascular endothelial growth factor(VEGF)and laser treatment etc.,which can not solve the problem of persistent disease activity of nAMD.Repeated treatment increases the economic burden of patients,and also the incidence of complications,such as increased intraocular pressure and inflammatory reaction.In recent years,the extensive application of gene therapy has brought more possibilities for the treatment of nAMD.It takes virus as the vector,combines the cDNA of target genes with the vector,and realizes the expression of target genes in the host cell by making use of the virus infecting host cells.Based on the successful animal experiments,phaseⅠand phaseⅡclinical trials with pigment epithelium derived factor,RNA interference,soluble VEGF receptor 1,endostatin and angiostatin,anti-VEGF Fab,soluble CD59,aflibercept,complement factor I,etc.as targets have been conducted at home and abroad.Certain achievements have been made,but some problems are also exposed.In this paper,the mechanism,research progress of clinical trials and existing problems of gene therapy for nAMD were reviewed,and the prospect of gene therapy in the future was proposed.
作者
张玮(综述)
颜华(审校)
Zhang Wei;Yan Hua(Department of Ophthalmology,Tianjin Medical University General Hospital,Tianjin 300052,China)
出处
《中华实验眼科杂志》
CAS
CSCD
北大核心
2021年第8期749-754,共6页
Chinese Journal Of Experimental Ophthalmology
基金
国家自然科学基金重点项目(81830026)
天津市重大疾病防治科技重大专项(18ZXDBSY00030)。
作者简介
通信作者:颜华,Email:zyyyanhua@tmu.edu.cn。
