Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration

Mara C. Ebeling, Zhaohui Geng, Madilyn R. Stahl, Rebecca J. Kapphahn, Heidi Roehrich, Sandra R. Montezuma, Deborah A. Ferrington, James R. Dutton

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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.

Original languageEnglish (US)
Article number62
Issue number1
StatePublished - Jan 2022

Bibliographical note

Funding Information:
Funding: This research was funded by the National Institutes of Health/National Eye Institute (grant number R01EY028554 to D.A.F. and J.R.D., P30EY11374 to H.R.), Regenerative Medicine Minnesota (grant number 091718 TR009), an anonymous benefactor for Age-related Macular Degeneration Research, the Lindsay Family Foundation, and the Elaine and Robert Larson Endowed Research Chair (D.A.F.).

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • Age-related macular degeneration
  • Human-induced pluripotent stem cells
  • Personalized drug testing
  • Retinal pigment epithelium

PubMed: MeSH publication types

  • Journal Article


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