【摘要】 新生血管性眼底病包括新生血管性年龄相关性黄斑变性(nAMD)和糖尿病视网膜病变(DR)等。病理性新生血管渗漏及其继发的视网膜脱离等是导致患者视力受损的主要原因。抗血管内皮生长因子(Anti-VEGF)是新生血管性眼底病的一线治疗药物，但存在需要频繁眼内注射、患者依从性差等问题。目前nAMD、DR等新生血管性眼底病的发病率逐年升高，因此迫切需要找到更安全长效的治疗方式。近年来，基因治疗领域迅速发展，其治疗策略主要包括基因补充和基因编辑。基因治疗的作用机制可以概括为：纠正缺陷基因导致的病理改变，如引入外源性正常基因或直接在基因组水平上修饰异常基因。大量基础和临床研究证明基因治疗是安全且有效的。目前，数十项视网膜基因治疗的临床试验正在开展，除遗传性视网膜病变外，新生血管性眼底病也是热门研究领域。本文重点总结了近年来基因补充、成簇的规律间隔的短回文重复序列(CRISPR)及CRISPR相关蛋白9 (Cas9)系统在nAMD和DR中的应用。更多还原

【Abstract】 Neovascular fundus diseases mainly include neovascular age-related macular degeneration(nAMD) and diabetic retinopathy(DR). Pathological neovascular leakage and the subsequent retinal detachment are the main causes of severe visual impairment. Anti-vascular endothelial growth factor(VEGF) is the first-line treatment for neovascular fundus diseases, but it has shortcomings, such as the need for frequent intravitreal injections and poor patient compliance. With the annually increasing incidence of acquired neovascular fundus diseases like nAMD and DR, there is an urgent need for safer and more long-lasting treatment options. In recent years, the field of gene therapy has advanced rapidly, with therapeutic strategies mainly involving gene supplementation and editing. The mechanism underlying gene therapy can be succinctly described as the correction of pathological alterations induced by defective genes. This is achieved either by the introduction of exogenous functional genes to restore normal cellular processes or by directly editing aberrant genes at the genomic level. Extensive basic and clinical research has demonstrated that gene therapy is both safe and effective. There are dozens of clinical trials on retinal gene therapy being carried out currently, focusing not only on inherited retinal diseases but also on neovascular fundus diseases. In this article, the application of the gene supplementation, clustered regularly interspaced short palindromic repeats(CRISPR) and CRISPR-associated protein 9(Cas9) system in the treatment of nAMD and DR is summarized.更多还原