Patient-derived cornea organoid model to study metabolomic characterization of rare disease: aniridia-associated keratopathy
Abstract Background Aniridia is a rare panocular disease caused by gene mutation in the PAX6, which is essential for eye development. Aniridia is inherited in an autosomal dominant manner, but its phenotype can vary significantly among individuals with the same mutation. Animal models, such as droso...
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BMC
2025-01-01
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| Series: | BMC Ophthalmology |
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| Online Access: | https://doi.org/10.1186/s12886-024-03831-w |
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| author | Ali Can Koc Vedat Sari Gamze Kocak Tuba Recber Emirhan Nemutlu Daniel Aberdam Sinan Güven |
| author_facet | Ali Can Koc Vedat Sari Gamze Kocak Tuba Recber Emirhan Nemutlu Daniel Aberdam Sinan Güven |
| author_sort | Ali Can Koc |
| collection | DOAJ |
| description | Abstract Background Aniridia is a rare panocular disease caused by gene mutation in the PAX6, which is essential for eye development. Aniridia is inherited in an autosomal dominant manner, but its phenotype can vary significantly among individuals with the same mutation. Animal models, such as drosophila, zebrafish, and rodents, have been used to study aniridia through Pax6 deletions. Recently, patient-derived limbal epithelial stem cells (LESCs) and human-induced pluripotent stem cells (hiPSCs) have been used to model the disease in vitro, providing new insights into therapeutic strategies. Methods In this study, corneal organoids were generated from hiPSCs derived from aniridia patients with three different PAX6 nonsense mutations, allowing for a detailed comparison between diseased and healthy control models. These organoids structurally mimicked the human cornea and were used to investigate histologic and metabolomic differences between healthy and aniridia-derived samples. Results Untargeted metabolomic analysis revealed significant metabolic differences between wild-type (WT) and aniridia-associated keratopathy (AAK) hiPSCs. Further metabolomic profiling at different time points demonstrated distinct metabolic shifts, with amino acid metabolism pathways being consistently enriched in AAK organoids. Conclusions This study emphasizes the profound impact of AAK mutations on metabolism, particularly in amino acid biosynthesis and energy metabolism pathways. |
| format | Article |
| id | doaj-art-79de5829880644d59bd74cad7169c0b2 |
| institution | Kabale University |
| issn | 1471-2415 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Ophthalmology |
| spelling | doaj-art-79de5829880644d59bd74cad7169c0b22025-01-12T12:12:28ZengBMCBMC Ophthalmology1471-24152025-01-0125111710.1186/s12886-024-03831-wPatient-derived cornea organoid model to study metabolomic characterization of rare disease: aniridia-associated keratopathyAli Can Koc0Vedat Sari1Gamze Kocak2Tuba Recber3Emirhan Nemutlu4Daniel Aberdam5Sinan Güven6Izmir Biomedicine and Genome CenterIzmir Biomedicine and Genome CenterIzmir Biomedicine and Genome CenterDepartment of Analytical Chemistry, Faculty of Pharmacy, Hacettepe UniversityDepartment of Analytical Chemistry, Faculty of Pharmacy, Hacettepe UniversityINSERM U1138, Centre de Recherche Des Cordeliers, Sorbonne Paris Cité UniversityIzmir Biomedicine and Genome CenterAbstract Background Aniridia is a rare panocular disease caused by gene mutation in the PAX6, which is essential for eye development. Aniridia is inherited in an autosomal dominant manner, but its phenotype can vary significantly among individuals with the same mutation. Animal models, such as drosophila, zebrafish, and rodents, have been used to study aniridia through Pax6 deletions. Recently, patient-derived limbal epithelial stem cells (LESCs) and human-induced pluripotent stem cells (hiPSCs) have been used to model the disease in vitro, providing new insights into therapeutic strategies. Methods In this study, corneal organoids were generated from hiPSCs derived from aniridia patients with three different PAX6 nonsense mutations, allowing for a detailed comparison between diseased and healthy control models. These organoids structurally mimicked the human cornea and were used to investigate histologic and metabolomic differences between healthy and aniridia-derived samples. Results Untargeted metabolomic analysis revealed significant metabolic differences between wild-type (WT) and aniridia-associated keratopathy (AAK) hiPSCs. Further metabolomic profiling at different time points demonstrated distinct metabolic shifts, with amino acid metabolism pathways being consistently enriched in AAK organoids. Conclusions This study emphasizes the profound impact of AAK mutations on metabolism, particularly in amino acid biosynthesis and energy metabolism pathways.https://doi.org/10.1186/s12886-024-03831-wAniridiaPax6HiPSCs (Human induced pluripotent stem cells)Cornea organoidsMetabolomicsAniridia-associated keratopathy (AAK) |
| spellingShingle | Ali Can Koc Vedat Sari Gamze Kocak Tuba Recber Emirhan Nemutlu Daniel Aberdam Sinan Güven Patient-derived cornea organoid model to study metabolomic characterization of rare disease: aniridia-associated keratopathy BMC Ophthalmology Aniridia Pax6 HiPSCs (Human induced pluripotent stem cells) Cornea organoids Metabolomics Aniridia-associated keratopathy (AAK) |
| title | Patient-derived cornea organoid model to study metabolomic characterization of rare disease: aniridia-associated keratopathy |
| title_full | Patient-derived cornea organoid model to study metabolomic characterization of rare disease: aniridia-associated keratopathy |
| title_fullStr | Patient-derived cornea organoid model to study metabolomic characterization of rare disease: aniridia-associated keratopathy |
| title_full_unstemmed | Patient-derived cornea organoid model to study metabolomic characterization of rare disease: aniridia-associated keratopathy |
| title_short | Patient-derived cornea organoid model to study metabolomic characterization of rare disease: aniridia-associated keratopathy |
| title_sort | patient derived cornea organoid model to study metabolomic characterization of rare disease aniridia associated keratopathy |
| topic | Aniridia Pax6 HiPSCs (Human induced pluripotent stem cells) Cornea organoids Metabolomics Aniridia-associated keratopathy (AAK) |
| url | https://doi.org/10.1186/s12886-024-03831-w |
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