Mitochondrial deletions in normal and degenerating rat retina.
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 (Bcl-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.
Bravo-Nuevo
Arturo
A
Institute for Biomedical Research, Department of Anatomy and Histology, University of Sydney, Sydney, NSW, Australia 2006. arturo@anatomy.usyd.edu
Williams
Neal
N
Geller
Scott
S
Stone
Jonathan
J
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism
D004272:DNA, Mitochondrial