Pathophysiology of the Optic Neuropathy Associated With Friedreich Ataxia

Objectives: 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. Conclusion: 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.