[关键词]
[摘要]
眼底疾病基因治疗研究近年来取得显著进展，为多种难治性眼病带来新希望。文章系统梳理了该领域最新研究进展，评估当前挑战并展望未来趋势，重点介绍了遗传性视网膜病变的基因治疗研究，包括RPE65-LCA基因治疗的商业化应用、视网膜色素变性(RP)多种亚型和Stargardt病的临床进展，以及Leber遗传性视神经病变(LHON)基因治疗的“双眼效应”现象。同时探讨了年龄相关性黄斑变性(ARMD)和糖尿病视网膜病变(DR)等复杂眼底病变的基因治疗策略，分析了基因递送系统的技术进展，包括AAV载体改造、非病毒载体和CRISPR/Cas9技术应用。文章还讨论了眼底疾病基因治疗面临的安全性、免疫原性、长期疗效和个体化策略等挑战。研究表明，眼底疾病基因治疗正从概念验证迈向临床应用，随着技术创新和经验积累，有望为患者提供精准治疗方案，显著改善视功能预后。
[Key word]
[Abstract]
Gene therapy research for fundus diseases has made significant progress recently, offering new hope for refractory ocular conditions. This review summarizes the latest developments, evaluates challenges, and explores future trends. Gene therapies for inherited retinal diseases, including commercialized RPE65-LCA therapy, clinical advances in retinitis pigmentosa(RP)subtypes and Stargardt disease, and the “bilateral effect” in Leber hereditary optic neuropathy(LHON)therapy, were highlighted in this review. Gene therapy strategies for complex disorders such as age-related macular degeneration(ARMD)and diabetic retinopathy(DR)were discussed. Advances in gene delivery systems, including adeno-associated virus(AAV)vectors, non-viral vectors, and CRISPR/Cas9 applications, were also analyzed. Furthermore, major challenges, including safety, immunogenicity, long-term efficacy, and personalized approaches were also discussed. Research indicates fundus gene therapy is transitioning from proof-of-concept to clinical application. With continued innovation and experience, it promises to provide precise treatment options, significantly improving visual outcomes for patients.
[中图分类号]
[基金项目]
浙江省医药卫生科技计划(No.2024KY366)
