Primary cultures of retinal pigment epithelium (RPE) from human adult donors (haRPE) and induced pluripotent stem cell derived-RPE (iPSC-RPE) are valuable model systems for gaining mechanistic insight and for testing potential therapies for age-related macular degeneration (AMD). This study evaluated the treatment response of haRPE and iPSC-RPE to oxidative stress and potential therapeutics addressing mitochondrial defects. haRPE and iSPC-RPE were derived from donors with or without AMD. Mitochondrial function was measured after treatment with menadione, AICAR, or trehalose and the response to treatment was compared between cell models and by disease status. In a subset of samples, haRPE and iPSC-RPE were generated from the same human donor to make a side-by-side comparison of the two cell models’ response to treatment. Disease-specific responses to all three treatments was observed in the haRPE. In contrast, iPSC-RPE had a similar response to all treatments irrespective of disease status. Analysis of haRPE and iPSC-RPE generated from the same human donor showed a similar response for donors without AMD, but there were significant differences in treatment response between cell models generated from AMD donors. These results support the use of iPSC-RPE and haRPE when investigating AMD mechanisms and new therapeutics but indicates that attention to experimental conditions is required.
Bibliographical noteFunding Information:
This work was supported in part by the National Institutes of Health (NIH) National Eye Institute (NEI) F31-EY031558 (to CRF), T32-EY025187 (to CRF), R01EY026012 (to DAF), and R01EY028554 (to DAF and JRD), NIH National Institute of Aging (NIA) T32-AG029796 (to CRF), Diana Jacobs Kalman/AFAR Scholarships for Research in the Biology of Aging (to CRF), VitreoRetinal Surgery Foundation Fellowship (to CRF), the Elaine and Robert Larson Endowed Vision Chair, the Lindsay Family Foundation, and an anonymous benefactor for AMD research.
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
- Age-related macular degeneration
- Oxida-tive stress
- Retinal pigment epithelium
PubMed: MeSH publication types
- Journal Article