Leber’s Hereditary Optic Neuropathy
Leber’s hereditary optic neuropathy (LHON) is a maternally inherited blinding disease with variable penetrance. Three primary mitochondrial DNA mutations, affecting the respiratory complex I, are necessary but not sufficient to cause blindness. Reduced efficiency of ATP synthesis and increased oxidative stress are believed to sensitize the retinal ganglion cells to apoptosis. Different therapeutic strategies are considered to counteract this pathogenic mechanism. However, potential treatments for the visual loss are complicated by the fact that patients are unlikely to benefit after optic atrophy occurs. There is no proven therapy to prevent or reverse the optic neuropathy in LHON. Results from a recent trial with idebenone hold promise to limit neurodegeneration and improve final outcome, promoting recovery of visual acuity. Other therapeutic options are under scrutiny, including gene therapy, agents increasing mitochondrial biogenesis, and anti-apoptotic drugs.
References and Recommended Reading
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- 30.Mahidol University: A randomized, double-blind, placebo-controlled trial of curcumin in Leber’s hereditary optic neuropathy (LHON). In: ClinicalTrials.gov [Internet}. Bethesda, MD: National Library of Medicine (US). Available from: http://clinicaltrials.gov/ct2/show/study/NCT00528151.
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- 44.••Giordano C, Montopoli M, Perli E, et al.: Estrogens ameliorate mitochondrial dysfunction in Leber’s hereditary optic neuropathy. Brain 2010, in press. This study demonstrated the role of estrogens in compensating for mitochondrial dysfunction in LHON and explains the reduced penetrance in females.Google Scholar