Related Experiment Video
Updated: Jan 3, 2026
Subretinal Transplantation of Human Embryonic Stem Cell-Derived Retinal Tissue in a Feline Large Animal Model
Published on: August 5, 2021
Retinal disease in ciliopathies: Recent advances with a focus on stem cell-based therapies
Holly Yu Chen1, Emily Welby1, Tiansen Li1
1Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Abstract:
Ciliopathies display extensive genetic and clinical heterogeneity, varying in severity, age of onset, disease progression and organ systems affected. Retinal involvement, as demonstrated by photoreceptor dysfunction or death, is a highly penetrant phenotype among a vast majority of ciliopathies. Photoreceptor cells possess a specialized and modified sensory cilium with membrane discs where efficient photon capture and ensuing signaling cascade initiate the visual process. Disruptions of cilia biogenesis and protein transport lead to impairment of photoreceptor function and eventually degeneration. Despite advances in elucidation of ciliogenesis and photoreceptor cilia defects, we have limited understanding of pathogenic mechanisms underlying retinal phenotype(s) observed in human ciliopathies. Patient-derived induced pluripotent stem cell (iPSC)-based approaches offer a unique opportunity to complement studies with model organisms and examine cilia disease relevant to humans. Three-dimensional retinal organoids from iPSC lines feature laminated cytoarchitecture, apical-basal polarity and emergence of a ciliary structure, thereby permitting pathogenic modeling of human photoreceptors in vitro. Here, we review the biology of photoreceptor cilia and associated defects and discuss recent progress in evolving treatment modalities, especially using patient-derived iPSCs, for retinal ciliopathies.
Insights
Ciliopathies cause vision loss by affecting photoreceptor cells and their cilia. Patient-derived stem cells and retinal organoids offer new ways to study these complex retinal diseases.
Area of Science:
- Ophthalmology
- Genetics
- Cell Biology
Background:
- Ciliopathies are genetic disorders with diverse clinical presentations and severity.
- Retinal dysfunction, including photoreceptor degeneration, is a common and severe phenotype in ciliopathies.
- Photoreceptor cilia are crucial for vision, and their defects impair function and lead to degeneration.
Purpose of the Study:
- To review the biology of photoreceptor cilia and associated defects in ciliopathies.
- To discuss the pathogenic mechanisms underlying retinal phenotypes in human ciliopathies.
- To highlight the potential of patient-derived induced pluripotent stem cells (iPSCs) for modeling and treating retinal ciliopathies.
Main Methods:
- Review of existing literature on ciliopathies, photoreceptor cilia biology, and iPSC-based research.
- Discussion of pathogenic mechanisms derived from model organisms and human studies.
- Examination of 3D retinal organoid models derived from iPSCs for studying photoreceptor function.
Main Results:
- Photoreceptor cilia are specialized structures essential for vision.
- Defects in cilia biogenesis and protein transport lead to photoreceptor dysfunction and degeneration.
- Patient-derived iPSC-based retinal organoids recapitulate key features of human photoreceptors, enabling in vitro disease modeling.
Conclusions:
- Understanding photoreceptor cilia biology is key to addressing retinal ciliopathies.
- Patient-derived iPSC technology provides a powerful platform for investigating disease mechanisms and developing therapies for retinal ciliopathies.
- Further research using iPSC-derived models is crucial for advancing treatment strategies for these vision-impairing genetic disorders.
Related Concept Videos
01:22iPS Cell Differentiation
01:13Induced Pluripotent Stem Cells