Pathophysiology of the optic neuropathy associated with Friedreich ataxia.
OBJECTIVE
To describe the optic neuropathy associated with the genetic defect in Friedreich ataxia and suggest a pathophysiologic mechanism.


METHODS
An experimental model of retinal ganglion cell death in the presence of metal chelation was used to test a hypothetical mechanism for the optic neuropathy of Friedreich ataxia.


RESULTS
Study of cultured rat retinal ganglion cells suggests that abnormal regulation of intracellular iron levels could increase sensitivity to reactive oxygen species and lead to cell death in these metabolically active tissues.


CONCLUSIONS
We hypothesize that decreased expression of frataxin, the mutated gene in Friedreich ataxia, could cause an optic neuropathy by increasing the sensitivity of retinal ganglion cells to oxidative stress.
Alldredge
Claron D
CD
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, 53792, USA.
Schlieve
Christopher R
CR
Miller
Neil R
NR
Levin
Leonard A
LA
D000818:Animals; D000831:Animals, Newborn; D000840:Anisoles; D016923:Cell Death; D002478:Cells, Cultured; D002712:Chlorides; D003676:Deferoxamine / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D005456:Fluorescent Dyes; D005621:Friedreich Ataxia / Q000378:metabolism / Q000503:physiopathology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D033862:Iron-Binding Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009901:Optic Nerve Diseases / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects; D011753:Pyrones; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000494:pharmacology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000096923:Frataxin
D000840:Anisoles; D002712:Chlorides; D003676:Deferoxamine; D005290:Ferric Compounds; D005296:Ferrous Compounds; D005456:Fluorescent Dyes; D007502:Iron Chelating Agents; D033862:Iron-Binding Proteins; D011753:Pyrones; D017382:Reactive Oxygen Species; D000096923:Frataxin; C472145:dihydroyangonin; C020748:ferrous sulfate; C024555:ferric chloride