Aier Eye Institute, Changsha, 410015, China.
Eye Center of Xiangya Hospital, Central South University, Changsha, 410008, China.
Stem Cell Res Ther. 2023 Nov 27;14(1):340. doi: 10.1186/s13287-023-03564-5.
Inherited retinal diseases (IRDs) can induce severe sight-threatening retinal degeneration and impose a considerable economic burden on patients and society, making efforts to cure blindness imperative. Transgenic animals mimicking human genetic diseases have long been used as a primary research tool to decipher the underlying pathogenesis, but there are still some obvious limitations. As an alternative strategy, patient-derived induced pluripotent stem cells (iPSCs), particularly three-dimensional (3D) organoid technology, are considered a promising platform for modeling different forms of IRDs, including retinitis pigmentosa, Leber congenital amaurosis, X-linked recessive retinoschisis, Batten disease, achromatopsia, and best vitelliform macular dystrophy. Here, this paper focuses on the status of patient-derived iPSCs and organoids in IRDs in recent years concerning disease modeling and therapeutic exploration, along with potential challenges for translating laboratory research to clinical application. Finally, the importance of human iPSCs and organoids in combination with emerging technologies such as multi-omics integration analysis, 3D bioprinting, or microfluidic chip platform are highlighted. Patient-derived retinal organoids may be a preferred choice for more accurately uncovering the mechanisms of human retinal diseases and will contribute to clinical practice.
遗传性视网膜疾病(IRDs)可导致严重的视力威胁性视网膜变性,并给患者和社会带来相当大的经济负担,因此努力治愈失明是当务之急。模拟人类遗传疾病的转基因动物长期以来一直被用作研究的主要工具,以揭示潜在的发病机制,但仍存在一些明显的局限性。作为一种替代策略,患者来源的诱导多能干细胞(iPSCs),特别是三维(3D)类器官技术,被认为是模拟不同形式 IRDs 的有前途的平台,包括色素性视网膜炎、先天性黑蒙 Leber、X 连锁隐性视网膜劈裂症、神经鞘脂沉积症、色盲和 Best 先天性黄斑营养不良。本文主要关注近年来患者来源的 iPSCs 和类器官在 IRDs 中的疾病建模和治疗探索方面的研究进展,以及将实验室研究转化为临床应用的潜在挑战。最后,强调了人类 iPSCs 和类器官与新兴技术(如多组学整合分析、3D 生物打印或微流控芯片平台)相结合的重要性。患者来源的视网膜类器官可能是更准确揭示人类视网膜疾病机制的首选方法,并将有助于临床实践。