Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside
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...
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| Format: | Article |
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Wiley
2011-01-01
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| Series: | Journal of Ophthalmology |
| Online Access: | http://dx.doi.org/10.1155/2011/179412 |
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| author | Rajeshwari D. Koilkonda John Guy |
| author_facet | Rajeshwari D. Koilkonda John Guy |
| author_sort | Rajeshwari D. Koilkonda |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e62dca84414a48789467b5a8cb49cc07 |
| institution | Kabale University |
| issn | 2090-004X 2090-0058 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Ophthalmology |
| spelling | doaj-art-e62dca84414a48789467b5a8cb49cc072025-02-03T06:05:25ZengWileyJournal of Ophthalmology2090-004X2090-00582011-01-01201110.1155/2011/179412179412Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to BedsideRajeshwari D. Koilkonda0John Guy1Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USABascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USALeber'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.http://dx.doi.org/10.1155/2011/179412 |
| spellingShingle | Rajeshwari D. Koilkonda John Guy Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside Journal of Ophthalmology |
| title | Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside |
| title_full | Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside |
| title_fullStr | Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside |
| title_full_unstemmed | Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside |
| title_short | Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside |
| title_sort | leber s hereditary optic neuropathy gene therapy from benchtop to bedside |
| url | http://dx.doi.org/10.1155/2011/179412 |
| work_keys_str_mv | AT rajeshwaridkoilkonda lebershereditaryopticneuropathygenetherapyfrombenchtoptobedside AT johnguy lebershereditaryopticneuropathygenetherapyfrombenchtoptobedside |