Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.
Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
Adv Exp Med Biol. 2023;1415:549-554. doi: 10.1007/978-3-031-27681-1_80.
Inherited retinal degenerations (IRD) encompasses a group of heterogeneous disorders causing debilitating visual diseases and blindness, affecting more than two million people worldwide, in all age groups. The inheritance patterns vary from autosomal dominant, autosomal recessive, X-linked, and sporadic with mutations in over 260 genes identified to date. Despite the significant advances in clinical diagnosis, there is no effective treatment available. Human-induced pluripotent stem cells (hiPSC) derived in vitro 3D retinal organoids offer a powerful preclinical tool to investigate the molecular mechanism(s) of inherited diseases. Organoids have the potential for the development of personalized therapies by modeling the disease-specific and patient-specific IRD. This mini-review will elaborate on the utility of the advanced culture model system by focusing on staging the in vitro human retinogenesis, modeling retinal diseases, and as a tool for testing potential therapeutic approaches to restore or prevent vision loss in affected individuals.
遗传性视网膜变性（IRD）是一组异质性疾病，可导致使人衰弱的视觉疾病和失明，影响全球所有年龄段的超过 200 万人。遗传模式从常染色体显性遗传、常染色体隐性遗传、X 连锁遗传和散发性遗传不等，迄今为止已鉴定出超过 260 个基因突变。尽管临床诊断取得了重大进展，但目前尚无有效的治疗方法。体外诱导多能干细胞（hiPSC）衍生的 3D 视网膜类器官为研究遗传性疾病的分子机制提供了有力的临床前工具。类器官通过对特定疾病和特定个体的 IRD 进行建模，具有开发个性化治疗方法的潜力。本综述将详细阐述先进的培养模型系统的实用性，重点介绍体外人视网膜发生的分期、视网膜疾病的建模以及作为测试潜在治疗方法的工具，以恢复或预防受影响个体的视力丧失。
