Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration

Neurobiol Aging. 2006 Jul;27(7):983-93. doi: 10.1016/j.neurobiolaging.2005.05.012. Epub 2005 Jun 23.


Mitochondrial dysfunctions have been implicated in the pathophysiology of several age-related diseases including age-related macular degeneration (AMD), a progressive neurodegenerative disease affecting primarily the retinal pigment epithelium (RPE). The aims of our electron microscopic and morphometric studies were to reveal qualitative and quantitative alterations of mitochondria in human RPE from AMD and from age- and sex-matched controls. With increasing age a significant decrease in number and area of mitochondria, as well as loss of cristae and matrix density were found in both AMD and control specimens. These decreases were significantly greater in AMD than in normal aging. Alterations of mitochondria were accompanied by proliferation of peroxisomes and lipofuscin granules in both AMD and control specimens, although the difference between groups was significant only for peroxisomes. Unexpectedly, morphometric data showed that the RPE alterations seen in AMD may also develop in normal aging, 10-15 years after appearing in AMD patients. These findings suggest that (i) the severity of mitochondrial and peroxisomal alterations are different between AMD and normal aging, and (ii) the timing of damage to RPE may be critical for the development of AMD. We conclude that besides the well-documented age-related changes in mitochondrial DNA, alterations of mitochondrial membranes may also play a role in the pathogenesis of AMD. These membranes could be a new target for treatment of AMD and other age-related diseases.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / metabolism
  • Aging / pathology*
  • Child
  • Child, Preschool
  • Cytoplasmic Granules / metabolism
  • Cytoplasmic Granules / pathology
  • Disease Progression
  • Energy Metabolism / physiology
  • Female
  • Humans
  • Lipofuscin / metabolism
  • Macular Degeneration / metabolism
  • Macular Degeneration / pathology*
  • Macular Degeneration / physiopathology
  • Male
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Membranes / pathology*
  • Peroxisomes / metabolism
  • Peroxisomes / pathology
  • Pigment Epithelium of Eye / metabolism
  • Pigment Epithelium of Eye / pathology*
  • Pigment Epithelium of Eye / physiopathology


  • Lipofuscin