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Journal of Ophthalmology
Volume 2011 (2011), Article ID 179412, 16 pages
Review Article

Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside

1Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
2McKnight Vision Research Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA

Received 30 June 2010; Revised 7 October 2010; Accepted 12 November 2010

Academic Editor: Radha Ayyagari

Copyright © 2011 Rajeshwari D. Koilkonda and John Guy. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disorder caused by point mutations in mitochondrial DNA (mtDNA). Most cases are due to mutations in genes encoding subunits of the NADH-ubiquinone oxidoreductase that is Complex I of the electron transport chain (ETC). These mutations are located at nucleotide positions 3460, 11778, or 14484 in the mitochondrial genome. The disease is characterized by apoplectic, bilateral, and severe visual loss. While the mutated mtDNA impairs generation of ATP by all mitochondria, there is only a selective loss of retinal ganglion cells and degeneration of optic nerve axons. Thus, blindness is typically permanent. Half of the men and 10% of females who harbor the pathogenic mtDNA mutation actually develop the phenotype. This incomplete penetrance and gender bias is not fully understood. Additional mitochondrial and/or nuclear genetic factors may modulate the phenotypic expression of LHON. In a population-based study, the mtDNA background of haplogroup J was associated with an inverse relationship of low-ATP generation and increased production of reactive oxygen species (ROS). Effective therapy for LHON has been elusive. In this paper, we describe the findings of pertinent published studies and discuss the controversies of potential strategies to ameliorate the disease.