Retinal Ciliopathies and Potential Gene Therapies: A Focus on Human iPSC-Derived Organoid Models
The human photoreceptor function is dependent on a highly specialised cilium. Perturbation of cilial function can often lead to death of the photoreceptor and loss of vision. Retinal ciliopathies are a genetically diverse range of inherited retinal disorders affecting aspects of the photoreceptor ci...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/5/2887 |
| _version_ | 1797264342427631616 |
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| author | Andrew McDonald Jan Wijnholds |
| author_facet | Andrew McDonald Jan Wijnholds |
| author_sort | Andrew McDonald |
| collection | DOAJ |
| description | The human photoreceptor function is dependent on a highly specialised cilium. Perturbation of cilial function can often lead to death of the photoreceptor and loss of vision. Retinal ciliopathies are a genetically diverse range of inherited retinal disorders affecting aspects of the photoreceptor cilium. Despite advances in the understanding of retinal ciliopathies utilising animal disease models, they can often lack the ability to accurately mimic the observed patient phenotype, possibly due to structural and functional deviations from the human retina. Human-induced pluripotent stem cells (hiPSCs) can be utilised to generate an alternative disease model, the 3D retinal organoid, which contains all major retinal cell types including photoreceptors complete with cilial structures. These retinal organoids facilitate the study of disease mechanisms and potential therapies in a human-derived system. Three-dimensional retinal organoids are still a developing technology, and despite impressive progress, several limitations remain. This review will discuss the state of hiPSC-derived retinal organoid technology for accurately modelling prominent retinal ciliopathies related to genes, including <i>RPGR</i>, <i>CEP290</i>, <i>MYO7A</i>, and <i>USH2A</i>. Additionally, we will discuss the development of novel gene therapy approaches targeting retinal ciliopathies, including the delivery of large genes and gene-editing techniques. |
| first_indexed | 2024-04-25T00:27:23Z |
| format | Article |
| id | doaj.art-145e863f94a74ec88791ff6b67ee6fa8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-25T00:27:23Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-145e863f94a74ec88791ff6b67ee6fa82024-03-12T16:46:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01255288710.3390/ijms25052887Retinal Ciliopathies and Potential Gene Therapies: A Focus on Human iPSC-Derived Organoid ModelsAndrew McDonald0Jan Wijnholds1Department of Ophthalmology, Leiden University Medical Center (LUMC), 2333 ZC Leiden, The NetherlandsDepartment of Ophthalmology, Leiden University Medical Center (LUMC), 2333 ZC Leiden, The NetherlandsThe human photoreceptor function is dependent on a highly specialised cilium. Perturbation of cilial function can often lead to death of the photoreceptor and loss of vision. Retinal ciliopathies are a genetically diverse range of inherited retinal disorders affecting aspects of the photoreceptor cilium. Despite advances in the understanding of retinal ciliopathies utilising animal disease models, they can often lack the ability to accurately mimic the observed patient phenotype, possibly due to structural and functional deviations from the human retina. Human-induced pluripotent stem cells (hiPSCs) can be utilised to generate an alternative disease model, the 3D retinal organoid, which contains all major retinal cell types including photoreceptors complete with cilial structures. These retinal organoids facilitate the study of disease mechanisms and potential therapies in a human-derived system. Three-dimensional retinal organoids are still a developing technology, and despite impressive progress, several limitations remain. This review will discuss the state of hiPSC-derived retinal organoid technology for accurately modelling prominent retinal ciliopathies related to genes, including <i>RPGR</i>, <i>CEP290</i>, <i>MYO7A</i>, and <i>USH2A</i>. Additionally, we will discuss the development of novel gene therapy approaches targeting retinal ciliopathies, including the delivery of large genes and gene-editing techniques.https://www.mdpi.com/1422-0067/25/5/2887retinal ciliopathyretinal organoidciliumgene therapyCRISPR/Cas9adeno-associated virus (AAV) |
| spellingShingle | Andrew McDonald Jan Wijnholds Retinal Ciliopathies and Potential Gene Therapies: A Focus on Human iPSC-Derived Organoid Models International Journal of Molecular Sciences retinal ciliopathy retinal organoid cilium gene therapy CRISPR/Cas9 adeno-associated virus (AAV) |
| title | Retinal Ciliopathies and Potential Gene Therapies: A Focus on Human iPSC-Derived Organoid Models |
| title_full | Retinal Ciliopathies and Potential Gene Therapies: A Focus on Human iPSC-Derived Organoid Models |
| title_fullStr | Retinal Ciliopathies and Potential Gene Therapies: A Focus on Human iPSC-Derived Organoid Models |
| title_full_unstemmed | Retinal Ciliopathies and Potential Gene Therapies: A Focus on Human iPSC-Derived Organoid Models |
| title_short | Retinal Ciliopathies and Potential Gene Therapies: A Focus on Human iPSC-Derived Organoid Models |
| title_sort | retinal ciliopathies and potential gene therapies a focus on human ipsc derived organoid models |
| topic | retinal ciliopathy retinal organoid cilium gene therapy CRISPR/Cas9 adeno-associated virus (AAV) |
| url | https://www.mdpi.com/1422-0067/25/5/2887 |
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