Perspective on AMD pathobiology: A bioenergetic crisis in the RPE

Cody R. Fisher, Deborah A. Ferrington

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

AMD is the leading cause of blindness in developed countries. The dry form of AMD, also known as atrophic AMD, is characterized by the death of RPE and photoreceptors. Currently, there are no treatments for this form of the disease due in part to our incomplete understanding of the mechanism causing AMD. Strong experimental evidence from studies of human donors with AMD supports the emerging hypothesis that defects in RPE mitochondria drive AMD pathology. These studies, using different experimental methods, have shown disrupted RPE mitochondrial architecture and decreased mitochondrial number and mass, altered content of multiple mitochondrial proteins, increased mitochondrial DNA damage that correlates with disease severity, and defects in bioenergetics for primary RPE cultures from AMD donors. Herein, we discuss a model of metabolic uncoupling that alters bioenergetics in the diseased retina and drives AMD pathology. These data provide the rationale for targeting the mitochondria in the RPE as the most efficacious intervention strategy if administered early, before vision loss and cell death.

Original languageEnglish (US)
Pages (from-to)AMD41-AMD47
JournalInvestigative Ophthalmology and Visual Science
Volume59
Issue number4
DOIs
StatePublished - Mar 2018

Bibliographical note

Funding Information:
The authors thank James Hurley and members of the Mitochondria Task Group at the 2016 meeting of the Ryan Initiative for Macula Research for their insightful discussions about retinal metabolism. Supported by National Institutes of Health/National Eye Institute Grants RO1 EY026012, RO1 EY028554 (DAF), and National Institute of Aging T32-AG029796 (CRF); an anonymous benefactor for AMD research; the Lindsay Family Foundation; the Elaine and Robert Larson Endowed Vision Research Chair; and an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology and Visual Neuroscience. Disclosure: C.R. Fisher, None; D.A. Ferrington, None

Publisher Copyright:
© 2018 The Authors.

Keywords

  • Human donor tissue
  • Mitochondria
  • Photoreceptors
  • Retinal metabolism
  • Retinal pigment epithelium

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