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Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration.
Cells. 2021 04 02; 10(4)C

Abstract

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.

Authors+Show Affiliations

Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA. Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.Histology Core for Vision Research, University of Minnesota, Minneapolis, MN 55455, USA.Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA. Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA. Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33918210

Citation

Ebeling, Mara C., et al. "Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium With the Complement Factor H Polymorphism for Age-Related Macular Degeneration." Cells, vol. 10, no. 4, 2021.
Ebeling MC, Geng Z, Kapphahn RJ, et al. Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration. Cells. 2021;10(4).
Ebeling, M. C., Geng, Z., Kapphahn, R. J., Roehrich, H., Montezuma, S. R., Dutton, J. R., & Ferrington, D. A. (2021). Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration. Cells, 10(4). https://doi.org/10.3390/cells10040789
Ebeling MC, et al. Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium With the Complement Factor H Polymorphism for Age-Related Macular Degeneration. Cells. 2021 04 2;10(4) PubMed PMID: 33918210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration. AU - Ebeling,Mara C, AU - Geng,Zhaohui, AU - Kapphahn,Rebecca J, AU - Roehrich,Heidi, AU - Montezuma,Sandra R, AU - Dutton,James R, AU - Ferrington,Deborah A, Y1 - 2021/04/02/ PY - 2021/03/02/received PY - 2021/03/26/revised PY - 2021/03/29/accepted PY - 2021/4/30/entrez PY - 2021/5/1/pubmed PY - 2021/5/1/medline KW - age-related macular degeneration KW - complement factor H KW - induced pluripotent stem cell KW - inflammation KW - mitochondrial function KW - retinal pigment epithelium JF - Cells JO - Cells VL - 10 IS - 4 N2 - 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. SN - 2073-4409 UR - https://www.unboundmedicine.com/medline/citation/33918210/Impaired_Mitochondrial_Function_in_iPSC_Retinal_Pigment_Epithelium_with_the_Complement_Factor_H_Polymorphism_for_Age_Related_Macular_Degeneration_ L2 - https://www.mdpi.com/resolver?pii=cells10040789 DB - PRIME DP - Unbound Medicine ER -