alpha-Tocopherol/lipid ratio in blood is decreased in patients with Leber's hereditary optic neuropathy and asymptomatic carriers of the 11778 mtDNA mutation

We examined achromatic contrast discrimination in asymptomatic carriers of 11778 Leber‘s hereditary optic neuropathy (LHON 18 controls) and 18 age-match were also tested. To evaluate magnocellular (MC) and Parvocellular (PC) contrast discrimination, we used a version of Pokorny and Smith's (1997) pulsed/steady-pedestal paradigms (PPP/SPP) thought to be detected via PC and MC pathways, respectively. A luminance pedestal (four 1° × 1° squares) was presented on a 12 cd/m2 surround. The luminance of one of the squares (trial square, TS) was randomly incremented for either 17 or 133 ms. Observers had to detect the TS, in a forced-choice task, at each duration, for three pedestal levels: 7, 12, 19 cd/m2. In the SPP, the pedestal was fixed, and the TS was modulated. For the PPP, all four pedestal squares pulsed for 17 or 133 ms, and the TS was simultaneously incremented or decremented. We found that contrast discrimination thresholds of LHON carriers were significantly higher than controls' in the condition with the highest luminance of both paradigms, implying impaired contrast processing with no evidence of differential sensitivity losses between the two systems. Carriers’ thresholds manifested significantly longer temporal integration than controls in the SPP, consistent with slowed MC responses. The SPP and PPP paradigms can identify contrast and temporal processing deficits in asymptomatic LHON carriers, and thus provide an additional tool for early detection and characterization of the disease.

Download Full-text

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

Journal of Ophthalmology ◽

10.1155/2011/179412 ◽

2011 ◽

Vol 2011 ◽

pp. 1-16 ◽

Cited By ~ 26

Author(s):

Rajeshwari D. Koilkonda ◽

John Guy

Keyword(s):

Optic Neuropathy ◽

Ganglion Cells ◽

Phenotypic Expression ◽

Point Mutations ◽

Population Based ◽

Incomplete Penetrance ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Mtdna Mutation ◽

Hereditary Optic Neuropathy

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.

Download Full-text

Colour vision defects in asymptomatic carriers of the Leber's hereditary optic neuropathy (LHON) mtDNA 11778 mutation from a large Brazilian LHON pedigree: a case-control study

British Journal of Ophthalmology ◽

10.1136/bjo.2005.074526 ◽

2006 ◽

Vol 90 (2) ◽

pp. 150-153 ◽

Cited By ~ 24

Author(s):

P A Quiros ◽

R J Torres ◽

S Salomao ◽

A Berezovsky ◽

V Carelli ◽

...

Keyword(s):

Optic Neuropathy ◽

Colour Vision ◽

Case Control Study ◽

Case Control ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Asymptomatic Carriers ◽

Vision Defects ◽

Control Study ◽

Hereditary Optic Neuropathy

Download Full-text

A case of neuromyelitis optica harboring both anti-aquaporin-4 antibodies and a pathogenic mitochondrial DNA mutation for Leber’s hereditary optic neuropathy

Multiple Sclerosis Journal ◽

10.1177/1352458513513057 ◽

2013 ◽

Vol 20 (2) ◽

pp. 258-260 ◽

Cited By ~ 8

Author(s):

Wataru Shiraishi ◽

Shintaro Hayashi ◽

Takashi Kamada ◽

Noriko Isobe ◽

Ryo Yamasaki ◽

...

Keyword(s):

Spinal Cord ◽

Mitochondrial Dna ◽

Neuromyelitis Optica ◽

Optic Neuropathy ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Mtdna Mutation ◽

Thoracic Spinal Cord ◽

Optic Nerves ◽

Hereditary Optic Neuropathy

We report the first case of definite neuromyelitis optica (NMO) with a pathogenic mitochondrial DNA (mtDNA) mutation for Leber’s hereditary optic neuropathy (LHON) (G11778A point mutation). A 36-year-old Japanese woman had experienced recurrent neurological symptoms originating from involvements of the optic nerves and spinal cord. She finally lost her bilateral vision, and spastic paraparesis and sensory disturbances below the T6 level remained despite intensive immunotherapies. Brain and spinal magnetic resonance imaging (MRI) revealed T2-high-intensity lesions in the optic nerves and thoracic spinal cord, but no lesions in the brain. A blood examination revealed positivity for both anti-aquaproin-4 antibodies and an LHON mtDNA mutation.

Download Full-text