Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. No universally effective treatments exist for atrophic or “dry” AMD, which results from loss of the retinal pigment epithelium (RPE) and photoreceptors and accounts for ≈80% of all AMD patients. Prior studies pr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/15/1/62 |
| _version_ | 1797491255635083264 |
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| author | Mara C. Ebeling Zhaohui Geng Madilyn R. Stahl Rebecca J. Kapphahn Heidi Roehrich Sandra R. Montezuma Deborah A. Ferrington James R. Dutton |
| author_facet | Mara C. Ebeling Zhaohui Geng Madilyn R. Stahl Rebecca J. Kapphahn Heidi Roehrich Sandra R. Montezuma Deborah A. Ferrington James R. Dutton |
| author_sort | Mara C. Ebeling |
| collection | DOAJ |
| description | Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. No universally effective treatments exist for atrophic or “dry” AMD, which results from loss of the retinal pigment epithelium (RPE) and photoreceptors and accounts for ≈80% of all AMD patients. Prior studies provide evidence for the involvement of mitochondrial dysfunction in AMD pathology. This study used induced pluripotent stem cell (iPSC) RPE derived from five AMD patients to test the efficacy of three drugs (AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide), Metformin, trehalose) that target key processes in maintaining optimal mitochondrial function. The patient iPSC-RPE lines were used in a proof-of-concept drug screen, utilizing an analysis of RPE mitochondrial function following acute and extended drug exposure. Results show considerable variability in drug response across patient cell lines, supporting the need for a personalized medicine approach for treating AMD. Furthermore, our results demonstrate the feasibility of using iPSC-RPE from AMD patients to develop a personalized drug treatment regime and provide a roadmap for the future clinical management of AMD. |
| first_indexed | 2024-03-10T00:44:51Z |
| format | Article |
| id | doaj.art-22a50d171ba84395a123b68ea9d38512 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T00:44:51Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-22a50d171ba84395a123b68ea9d385122023-11-23T15:01:29ZengMDPI AGPharmaceuticals1424-82472022-01-011516210.3390/ph15010062Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular DegenerationMara C. Ebeling0Zhaohui Geng1Madilyn R. Stahl2Rebecca J. Kapphahn3Heidi Roehrich4Sandra R. Montezuma5Deborah A. Ferrington6James R. Dutton7Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USADepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USADepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USAHistology Core for Vision Research, University of Minnesota, Minneapolis, MN 55455, USADepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USADepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USAAge-related macular degeneration (AMD) is the leading cause of blindness in the elderly. No universally effective treatments exist for atrophic or “dry” AMD, which results from loss of the retinal pigment epithelium (RPE) and photoreceptors and accounts for ≈80% of all AMD patients. Prior studies provide evidence for the involvement of mitochondrial dysfunction in AMD pathology. This study used induced pluripotent stem cell (iPSC) RPE derived from five AMD patients to test the efficacy of three drugs (AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide), Metformin, trehalose) that target key processes in maintaining optimal mitochondrial function. The patient iPSC-RPE lines were used in a proof-of-concept drug screen, utilizing an analysis of RPE mitochondrial function following acute and extended drug exposure. Results show considerable variability in drug response across patient cell lines, supporting the need for a personalized medicine approach for treating AMD. Furthermore, our results demonstrate the feasibility of using iPSC-RPE from AMD patients to develop a personalized drug treatment regime and provide a roadmap for the future clinical management of AMD.https://www.mdpi.com/1424-8247/15/1/62human-induced pluripotent stem cellsretinal pigment epitheliumage-related macular degenerationpersonalized drug testing |
| spellingShingle | Mara C. Ebeling Zhaohui Geng Madilyn R. Stahl Rebecca J. Kapphahn Heidi Roehrich Sandra R. Montezuma Deborah A. Ferrington James R. Dutton Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration Pharmaceuticals human-induced pluripotent stem cells retinal pigment epithelium age-related macular degeneration personalized drug testing |
| title | Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration |
| title_full | Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration |
| title_fullStr | Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration |
| title_full_unstemmed | Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration |
| title_short | Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration |
| title_sort | testing mitochondrial targeted drugs in ipsc rpe from patients with age related macular degeneration |
| topic | human-induced pluripotent stem cells retinal pigment epithelium age-related macular degeneration personalized drug testing |
| url | https://www.mdpi.com/1424-8247/15/1/62 |
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