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Mitochondrial Deletions in Normal and Degenerating Rat Retina

  • Arturo Bravo-Nuevo
  • Neal Williams
  • Scott Geller
  • Jonathan Stone
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 533)

Abstract

Photoreceptor death by apoptosis is the central pathology of most forms of retinal degeneration. Mitochondria play key roles in apoptosis, releasing both signals which induce apoptosis (cytochrome c, caspases) and signals which inhibit apoptosis (Bc1-2). Because mitochondria are the site of oxidative metabolism they are also a major site of formation of the toxic oxygen intermediates which form as oxygen is recruited into the oxidative phosphorylation pathway. Previous studies have shown that deletions in mtDNA accumulate in postmitotic tissues (central nervous, muscle) and that their accumulation is accelerated by oxidative stress (such as hypoxia) (Takeda et al. 1996;Lee et al. 1994; Merril et al. 1996; Englander et al. 1999). It seems possible therefore that mitochondria are a site at which oxidative stress induces the death of retinal neurones. This study investigates the accumulation of mtDNA deletions in the rat retina, in both normal (non-degenerative) and degenerative strains. Deletions were undetectable in Sprague-Dawley albino rats (24 months) but were detected at 15 months in the rapidly degenerating RCS strain. The appearance of deletions in the RCS strain, in which retinal oxygen tension is known to rise as the degeneration progresses, gives support to the ideas that oxidative stress is a factor in mtDNA deletions, and in the progress of the late stages of the degeneration.

Keywords

Retinal Degeneration Outer Retina Muller Cell Oxidative Phosphorylation Pathway Deletion Product 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Arturo Bravo-Nuevo
    • 1
  • Neal Williams
    • 1
  • Scott Geller
    • 2
  • Jonathan Stone
    • 1
  1. 1.Institute for Biomedical Research and the Department of Anatomy and HistologyUniversity of SydneySydneyAustralia
  2. 2.School of OptometryUniversity of CaliforniaBerkeleyUSA

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