Laboratory for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, Division of Ophthalmic Genetics, The Eye Hospital, Wenzhou Medical University, State Key Laboratory for Ophthalmology, Optometry & Visual Science, National Center for International Research in Regenerative Medicine and Neurogenetics, Wenzhou, 325027, China.
Laboratory for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, Division of Ophthalmic Genetics, The Eye Hospital, Wenzhou Medical University, State Key Laboratory for Ophthalmology, Optometry & Visual Science, National Center for International Research in Regenerative Medicine and Neurogenetics, Wenzhou, 325027, China.
Prog Retin Eye Res. 2019 Mar;69:38-56. doi: 10.1016/j.preteyeres.2018.11.003. Epub 2018 Nov 9.
Cell replacement therapy is a promising treatment for irreversible retinal cell death in diverse diseases, such as age-related macular degeneration (AMD), Stargardt's disease, retinitis pigmentosa (RP) and glaucoma. These diseases are all characterized by the degeneration of one or two retinal cell types that cannot regenerate spontaneously in humans. Aberrant retinal pigment epithelial (RPE) cells can be observed through optical coherence tomography (OCT) in AMD patients. In RP patients, the morphological and functional abnormalities of RPE and photoreceptor layers are caused by a genetic abnormality. Stargardt's disease or juvenile macular degeneration, which is characterized by the loss of the RPE and photoreceptors in the macular area, causes central vision loss at an early age. Loss of retinal ganglion cells (RGCs) can be observed in patients with glaucoma. Once the retinal cell degeneration is triggered, no treatments can reverse it. Transplantation-based approaches have been proposed as a universal therapy to target patients with various concomitant diseases. Both the replacement of dead cells and neuroprotection are strategies used to rescue visual function in animal models of retinal degeneration. Diverse retinal cell types derived from pluripotent stem cells, including RPE cells, photoreceptors, RGCs and even retinal organoids with a layered structure, provide unlimited cell sources for transplantation. In addition, mesenchymal stem cells (MSCs) are multifunctional and protect degenerating retinal cells. The aim of this review is to summarize current findings from preclinical and clinical studies. We begin with a brief introduction to retinal degenerative diseases and cell death in diverse diseases, followed by methods for retinal cell generation. Preclinical and clinical studies are discussed, and future concerns about efficacy, safety and immunorejection are also addressed.
细胞替代疗法是一种有前途的治疗方法，可用于治疗多种疾病引起的不可逆转的视网膜细胞死亡，例如年龄相关性黄斑变性（AMD）、斯塔加特病、色素性视网膜炎（RP）和青光眼。这些疾病的特征都是一种或两种视网膜细胞类型的退化，而在人类中这些细胞不能自发再生。通过光学相干断层扫描（OCT）可以观察到 AMD 患者的异常视网膜色素上皮（RPE）细胞。在 RP 患者中，RPE 和光感受器层的形态和功能异常是由遗传异常引起的。斯塔加特病或青少年黄斑变性，其特征是黄斑区的 RPE 和光感受器丧失，导致患者在早年出现中心视力丧失。青光眼患者可观察到视网膜神经节细胞（RGC）的丧失。一旦触发了视网膜细胞退化，就没有治疗方法可以逆转它。基于移植的方法已被提出作为一种通用疗法，适用于各种伴发疾病的患者。在视网膜变性的动物模型中，替代死亡细胞和神经保护都是用于挽救视觉功能的策略。多能干细胞来源的各种视网膜细胞类型，包括 RPE 细胞、光感受器、RGC 甚至具有分层结构的视网膜类器官，为移植提供了无限的细胞来源。此外，间充质干细胞（MSCs）具有多功能性，可以保护退化的视网膜细胞。本综述的目的是总结目前在临床前和临床研究中的发现。我们首先简要介绍了各种疾病中的视网膜退行性疾病和细胞死亡，然后介绍了视网膜细胞生成的方法。讨论了临床前和临床研究，并探讨了未来对疗效、安全性和免疫排斥的关注。
