Investigating mitochondrial fission, fusion, and autophagy in retinal pigment epithelium from donors with age-related macular degeneration

Cody R. Fisher, Adam A. Shaaeli, Mara C. Ebeling, Sandra R. Montezuma, Deborah A. Ferrington

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries, characterized by the death of retinal pigment epithelial (RPE) cells and photoreceptors. Previous studies report an accumulation of damaged and dysfunctional mitochondria in RPE of human donors with AMD. Understanding how damaged mitochondria accumulate in AMD is an important step in discovering disease mechanisms and identifying therapeutic targets. In this report, we assessed mitochondrial fission and fusion by quantifying proteins and measured mitochondrial autophagy (mitophagy) via protein analysis and advanced imaging techniques using mitochondrial targeted mKeima in primary human RPE from donors with or without AMD. We report disease-specific differences in mitochondrial proteins that regulate fission, fusion, and mitophagy that were present at baseline and with treatments to stimulate these pathways. Data suggest AMD RPE utilize receptor-mediated mitophagy as a compensatory mechanism for deficits in the ubiquitin-mediated mitophagy pathway. These changes in mitochondrial homeostasis could lead to the buildup of damaged and dysfunctional mitochondria observed in the RPE of AMD donors.

Original languageEnglish (US)
Article number21725
JournalScientific reports
Volume12
Issue number1
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
The authors wish to acknowledge the contribution of personnel from the Lions Gift of Sight (St. Paul, MN) for their assistance in procuring human donor eyes and processing eye tissue. The authors also thank the donors and their families for their essential contributions to the research. 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), 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), University of Minnesota Undergraduate Research Opportunities Program (to AAS), the Elaine and Robert Larson Endowed Vision Chair, the Lindsay Family Foundation, and an anonymous benefactor for AMD research.

Funding Information:
The authors wish to acknowledge the contribution of personnel from the Lions Gift of Sight (St. Paul, MN) for their assistance in procuring human donor eyes and processing eye tissue. The authors also thank the donors and their families for their essential contributions to the research. 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), 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), University of Minnesota Undergraduate Research Opportunities Program (to AAS), the Elaine and Robert Larson Endowed Vision Chair, the Lindsay Family Foundation, and an anonymous benefactor for AMD research.

Publisher Copyright:
© 2022, The Author(s).

PubMed: MeSH publication types

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

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