Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration
Age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is characterized by loss of the retinal pigment epithelium (RPE). While the disease mechanism remains unclear, prior studies have linked AMD with RPE mitochondrial defects and genetic polymorphisms in the comple...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/4/789 |
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| author | Mara C. Ebeling Zhaohui Geng Rebecca J. Kapphahn Heidi Roehrich Sandra R. Montezuma James R. Dutton Deborah A. Ferrington |
| author_facet | Mara C. Ebeling Zhaohui Geng Rebecca J. Kapphahn Heidi Roehrich Sandra R. Montezuma James R. Dutton Deborah A. Ferrington |
| author_sort | Mara C. Ebeling |
| collection | DOAJ |
| description | Age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is characterized by loss of the retinal pigment epithelium (RPE). While the disease mechanism remains unclear, prior studies have linked AMD with RPE mitochondrial defects and genetic polymorphisms in the complement pathway. This study used RPE generated from induced pluripotent stem cells (iPSC-RPE), which were derived from human donors with or without AMD and genotyped for the complement factor H (CFH) AMD high-risk allele (rs1061170, Y402H) to investigate whether donor disease state or genotype had a detrimental effect on mitochondrial function and inflammation. Results show that cells derived from donors with AMD display decreased mitochondrial function under conditions of stress and elevated expression of inflammatory markers compared to iPSC-RPE from individuals without AMD. A more pronounced reduction in mitochondrial function and increased inflammatory markers was observed in CFH high-risk cells, irrespective of disease state. These results provide evidence for a previously unrecognized link between CFH and mitochondrial function that could contribute to RPE loss in AMD patients harboring the CFH high-risk genotype. |
| first_indexed | 2024-03-10T12:39:21Z |
| format | Article |
| id | doaj.art-24ed703017774b60b67774d73b999e07 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T12:39:21Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-24ed703017774b60b67774d73b999e072023-11-21T13:58:06ZengMDPI AGCells2073-44092021-04-0110478910.3390/cells10040789Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular DegenerationMara C. Ebeling0Zhaohui Geng1Rebecca J. Kapphahn2Heidi Roehrich3Sandra R. Montezuma4James R. Dutton5Deborah A. Ferrington6Department 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, USAHistology Core for Vision Research, 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, USADepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USAAge-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is characterized by loss of the retinal pigment epithelium (RPE). While the disease mechanism remains unclear, prior studies have linked AMD with RPE mitochondrial defects and genetic polymorphisms in the complement pathway. This study used RPE generated from induced pluripotent stem cells (iPSC-RPE), which were derived from human donors with or without AMD and genotyped for the complement factor H (CFH) AMD high-risk allele (rs1061170, Y402H) to investigate whether donor disease state or genotype had a detrimental effect on mitochondrial function and inflammation. Results show that cells derived from donors with AMD display decreased mitochondrial function under conditions of stress and elevated expression of inflammatory markers compared to iPSC-RPE from individuals without AMD. A more pronounced reduction in mitochondrial function and increased inflammatory markers was observed in CFH high-risk cells, irrespective of disease state. These results provide evidence for a previously unrecognized link between CFH and mitochondrial function that could contribute to RPE loss in AMD patients harboring the CFH high-risk genotype.https://www.mdpi.com/2073-4409/10/4/789induced pluripotent stem cellretinal pigment epitheliumage-related macular degenerationcomplement factor Hmitochondrial functioninflammation |
| spellingShingle | Mara C. Ebeling Zhaohui Geng Rebecca J. Kapphahn Heidi Roehrich Sandra R. Montezuma James R. Dutton Deborah A. Ferrington Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration Cells induced pluripotent stem cell retinal pigment epithelium age-related macular degeneration complement factor H mitochondrial function inflammation |
| title | Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration |
| title_full | Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration |
| title_fullStr | Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration |
| title_full_unstemmed | Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration |
| title_short | Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration |
| title_sort | impaired mitochondrial function in ipsc retinal pigment epithelium with the complement factor h polymorphism for age related macular degeneration |
| topic | induced pluripotent stem cell retinal pigment epithelium age-related macular degeneration complement factor H mitochondrial function inflammation |
| url | https://www.mdpi.com/2073-4409/10/4/789 |
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