Autophagy and exomoses in the aged retinal pigment epithelium: Possible relevance to drusen formation and age-related macular degeneration

Ai Ling Wang, Thomas J. Lukas, Ming Yuan, Nga Du, Mark O M Tso, Arthur H. Neufeld

Research output: Contribution to journalArticle

Abstract

Age-related macular degeneration (AMD) is a major cause of loss of central vision in the elderly. The formation of drusen, an extracellular, amorphous deposit of material on Bruch's membrane in the macula of the retina, occurs early in the course of the disease. Although some of the molecular components of drusen are known, there is no understanding of the cell biology that leads to the formation of drusen. We have previously demonstrated increased mitochondrial DNA (mtDNA) damage and decreased DNA repair enzyme capabilities in the rodent RPE/choroid with age. In this study, we found that drusen in AMD donor eyes contain markers for autophagy and exosomes. Furthermore, these markers are also found in the region of Bruch's membrane in old mice. By in vitro modeling increased mtDNA damage induced by rotenone, an inhibitor of mitochondrial complex I, in the RPE, we found that the phagocytic activity was not altered but that there were: 1) increased autophagic markers, 2) decreased lysosomal activity, 3) increased exocytotic activity and 4) release of chemoattractants. Exosomes released by the stressed RPE are coated with complement and can bind complement factor H, mutations of which are associated with AMD. We speculate that increased autophagy and the release of intracellular proteins via exosomes by the aged RPE may contribute to the formation of drusen. Molecular and cellular changes in the old RPE may underlie susceptibility to genetic mutations that are found in AMD patients and may be associated with the pathogenesis of AMD in the elderly.

Original languageEnglish (US)
Article numbere4160
JournalPLoS One
Volume4
Issue number1
DOIs
StatePublished - Jan 8 2009

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Retinal Pigments
autophagy
Retinal Pigment Epithelium
Autophagy
Macular Degeneration
Mitochondrial DNA
exosomes
Exosomes
epithelium
pigments
Cytology
DNA Repair Enzymes
Membranes
Complement Factor H
Rotenone
Bruch Membrane
Chemotactic Factors
Deposits
DNA damage
DNA Damage

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Autophagy and exomoses in the aged retinal pigment epithelium : Possible relevance to drusen formation and age-related macular degeneration. / Wang, Ai Ling; Lukas, Thomas J.; Yuan, Ming; Du, Nga; Tso, Mark O M; Neufeld, Arthur H.

In: PLoS One, Vol. 4, No. 1, e4160, 08.01.2009.

Research output: Contribution to journalArticle

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