摘　要：视网膜极易因激光意外事故、中枢神经或视网膜退行性疾病发生异常改变，严重威胁视功能。目前，仍没有针对哺乳动物视网膜损伤的完善修复机制。视网膜“干细胞”穆勒胶质（MG）细胞不能自发进入细胞周期，基因编辑手段可使MG细胞转分化，从而具有视网膜祖细胞的能力。转分化相关信号通路及调控因子对MG基因组重编程至关重要。基因编辑治疗利用腺病毒、慢病毒等载体将外源基因导入体内，促使哺乳动物受损视网膜中MG细胞激增和去分化，损伤的视网膜神经元再生。与传统药物治疗需要长期服药相比，基因疗法的出现有望实现通过一次治疗达到修复目的。文章就视网膜修复机制、调控视神经再生的信号通路以及基因治疗修复损伤视网膜研究现状和应用过程中存在的问题进行综述，并展望未来相关的发展趋势。未来基因编辑治疗将会给视神经再生修复研究带来深刻变革，为视网膜疾病的治疗带来新的曙光。
关键词：视网膜损伤修复；视神经再生；视网膜祖细胞；基因治疗；基因编辑技术
中图分类号：Q81                                文献标志码：A               DOI：10.3969/j.issn.1007-7146.2023.05.004

Abstract: The retina is highly susceptible to abnormal changes due to laser accidents, central nervous system or retinal degenerative diseases, which can seriously threaten visual function. There is still no well-developed repair mechanism for mammalian retinal damage, and MG cells, the “stem cells” of the retina, cannot enter the cell cycle spontaneously, and MG cell transdifferentiation-related signalling pathways and regulatory factors play a crucial role in reprogramming the MG genome. Gene editing treatment of the retina enables the production of large numbers of neurons from MG cells in the damaged mammalian retina, replenishing damaged neurons and restoring vision. Gene editing therapy uses vectors such as adenovirus and lentivirus to introduce exogenous genes into the body to regenerate damaged retinal neurons. The advent of gene therapy holds the promise of achieving repair in a single treatment, as opposed to traditional drug treatments that require long-term medication. This article reviews the current status and problems in the application of gene therapy for retinal repair, the signalling pathways regulating optic nerve regeneration, and the future trends of gene therapy for retinal repair. In the future, gene editing therapy will bring profound changes to the research of optic nerve regeneration and repair, and bring a new dawn to the treatment of retinal diseases.
Key words: retinal damage repair; optic nerve regeneration; retinal progenitor cells；gene therapy; gene editing technology
（Acta Laser Biology Sinica, 2023, 32(5): 414-422）