Stem Cell Models Offer New Insight into Childhood Genetic Blindness

干细胞模型为儿童遗传性失明提供了新见解

November 21, 2025

2025年11月21日

Researchers at the Eye Genetics Research Unit at the Children's Medical Research Institute (CMRI) have become the first in the world to use stem cells to study one of the genetic causes of Leber Congenital Amaurosis (LCA), a rare inherited condition that causes severe vision loss in infants and young children.

儿童医学研究所（CMRI）眼科遗传学研究组的研究人员已成为世界上首个利用干细胞研究莱伯先天性黑蒙（LCA）的遗传原因之一的团队，这是一种罕见的遗传性疾病，会导致婴幼儿严重视力丧失。

Findings published in Stem Cell Reports indicate that gene therapy may soon provide a potential pathway to prevent blindness in affected patients..

发表在《干细胞报告》上的研究结果表明，基因疗法可能很快为预防受影响患者的失明提供一条潜在途径。

Modeling RPGRIP1-Related Retinal Disease

建模RPGRIP1相关的视网膜疾病

The study, led by Dr. To Ha Loi and colleagues, investigated RPGRIP1, a gene essential for the development and maintenance of photoreceptor cells, the light-sensitive cells that enable vision. Mutations in RPGRIP1 can lead to severe, currently untreatable retinal disease in children.

这项由何黎博士及其同事领导的研究调查了RPGRIP1基因，这是一种对感光细胞的发育和维持至关重要的基因，感光细胞是使视觉成为可能的光敏细胞。RPGRIP1基因的突变可能导致儿童严重的、目前无法治疗的视网膜疾病。

Many RPGRIP1 variants are still difficult to interpret. Nearly half of the known mutations are listed in the ClinVar database as having uncertain significance, limiting the ability of families and clinicians to confirm diagnoses or determine eligibility for clinical trials and future gene therapy programs..

许多 RPGRIP1 变异仍然难以解读。已知的突变中，几乎一半在 ClinVar 数据库中被列为意义不明，这限制了家庭和临床医生确认诊断或确定是否符合临床试验和未来基因治疗计划的资格。

Using Stem Cell–Derived Retinal Organoids

使用干细胞衍生的视网膜类器官

To address this challenge, the CMRI team developed 3D retinal organoids from stem cells, lab-grown mini retinas that replicate the structure and function of the human eye. These organoids allowed the researchers to study how RPGRIP1-related retinal disease develops and progresses at the cellular level..

为了应对这一挑战，CMRI团队利用干细胞开发了3D视网膜类器官，这些实验室培育的迷你视网膜能够复制人眼的结构和功能。这些类器官使研究人员能够在细胞层面研究与RPGRIP1相关的视网膜疾病是如何发展和进展的。

This study marks the first use of retinal organoids to model RPGRIP1-related disease using both patient-derived and genetically engineered cells. The team found that even in early-onset cases, the overall structure of the retina appeared preserved, indicating that gene therapy may still have potential to restore vision in affected children..

本研究标志着首次使用视网膜类器官通过患者来源和基因工程细胞来模拟与RPGRIP1相关的疾病。研究团队发现，即使在早发病例中，视网膜的整体结构似乎仍然得以保留，这表明基因治疗仍有可能恢复受影响儿童的视力。

Implications for Future Gene Therapy

未来基因治疗的潜在影响

Previous research into RPGRIP1-related disease relied primarily on animal models, such as mice. In contrast, the new human retinal organoids provide a more precise and scalable platform for studying inherited retinal disorders.

以往对 RPGRIP1 相关疾病的研究主要依赖于动物模型，如小鼠。相比之下，新的人类视网膜类器官为研究遗传性视网膜疾病提供了更精确且可扩展的平台。

The findings highlight the potential for gene therapy to address early vision loss caused by LCA, supporting continued research into treatment options for children with inherited retinal conditions.

研究结果强调了基因疗法在解决由LCA引起的早期视力丧失方面的潜力，支持对患有遗传性视网膜疾病的儿童的治疗选择进行持续研究。

Reference:

参考：

Connecting cilium, stress response and proteostasis abnormalities inform variant and therapy assessment in RPGRIP1 retinal organoids, Stem Cell Reports (2025). DOI: 10.1016/j.stemcr.2025.102717

连接纤毛、应激反应和蛋白质稳态异常为RPGRIP1视网膜类器官中的变异和治疗评估提供信息，《干细胞报告》（2025）。DOI: 10.1016/j.stemcr.2025.102717