Perspective on AMD pathobiology: A bioenergetic crisis in the RPE

Cody R. Fisher, Deborah A. Ferrington

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

Fingerprint

Energy Metabolism
Mitochondria
Pathology
Mitochondrial Proteins
Blindness
Mitochondrial DNA
Developed Countries
DNA Damage
Retina
Cell Death
Drive
Therapeutics

Keywords

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

PubMed: MeSH publication types

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

Cite this

Perspective on AMD pathobiology : A bioenergetic crisis in the RPE. / Fisher, Cody R.; Ferrington, Deborah A.

In: Investigative Ophthalmology and Visual Science, Vol. 59, No. 4, 03.2018, p. AMD41-AMD47.

Research output: Contribution to journalArticle

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