Leber Hereditary Optic Neuropathy: Review of Treatment and Management

Hage, Rabih; Vignal-Clermont, C.

doi:10.3389/fneur.2021.651639

Cited by 46 publications

(53 citation statements)

References 68 publications

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“…Leber's hereditary optic neuropathy (LHON) is the most common hereditary optic neuropathy with an average onset around age 20. Patients usually suffer from painless, subacute, or rapid vision loss in both eyes (Yu-Wai-Man and Chinnery, 1993 ; Yu-Wai-Man et al, 2009 ; Amore et al, 2021 ; Hage and Vignal-Clermont, 2021 ). LHON is caused by mitochondrial gene variations, and more than 30 pathogenic mutations have been found (Brandon et al, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

Multi-mtDNA Variants May Be a Factor Contributing to Mitochondrial Function Variety in the Skin-Derived Fibroblasts of Leber's Hereditary Optic Neuropathy Patients

Yao

Zhou

Yang

et al. 2022

Front. Mol. Neurosci.

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Heterogeneity is a major feature of Leber's hereditary optic neuropathy (LHON) and has a significant impact on the manifestation and diagnosis of the disease. This study explored whether multiple variations in mitochondrial genes were associated with the heterogeneity, mainly phenotypic heterogeneity. Ophthalmic examinations were conducted in two probands with LHON with G11778A and multiple mitochondrial DNA gene (mtDNA) variants. Skin fibroblast cell lines were generated from patients and age- and sex-matched controls. ROS levels, mitochondrial membrane potential, cell energy respiration, and metabolic functions were measured. Flow cytometry and cell viability tests were performed to evaluate the cell apoptosis levels and fate. We found that cells with more mtDNA variants had higher ROS levels, lower mitochondrial membrane potential, and weaker respiratory function. Flow cytometry and cell viability testing showed that multiple mtDNA variants are associated with different levels of cell viability and apoptosis. In conclusion, we found that skin-derived fibroblast cells from G11778A LHON patients could be used as models for LHON research. Multi-mtDNA variants contribute to mitochondrial function variety, which may be associated with heterogeneity in patients with LHON.

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Section: Introductionmentioning

confidence: 99%

Multi-mtDNA Variants May Be a Factor Contributing to Mitochondrial Function Variety in the Skin-Derived Fibroblasts of Leber's Hereditary Optic Neuropathy Patients

Yao

Zhou

Yang

et al. 2022

Front. Mol. Neurosci.

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“…There was no improvement in functional or in morpho-logical examinations during or at the end of treatment with Idebenone, even if the treatment was started shortly after presentation. Although the patient was positive for G11778A mutation, which is considered to have a good prognosis under treatment [16,19,20], we obtained no recovery in VA, visual field, VEP, fundoscopy, nor OCT after 12 months of therapy, so we stopped Idebenone treatment. The 19year-old brother was also positive for G11778A mutation, so we examine him every three months for an early diagnosis and proper initiation of treatment.…”

Section:  Discussionmentioning

confidence: 88%

Retinal morphological and functional response to Idebenone therapy in Leber hereditary optic neuropathy

Mercuţ¹,

Tănasie²,

Dan³

et al. 2022

Rom J Morphol Embryol

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Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to optic atrophy due to degeneration of the retinal ganglion cell. A curative treatment is not available at the moment, but a new antioxidant drug, Idebenone, is expected to reduce the progression of the disorder. Two male patients, genetically confirmed with LHON, were clinically, morphologically, and electrophysiologically evaluated, before and three, six, nine and 12 months after starting the treatment. The patient with 3460G>A mutation in mitochondrially-encoded nicotinamide adenine dinucleotide, reduced form (NADH):ubiquinone oxidoreductase core subunit (mtND)1 gene showed an improvement in visual acuity, visual field, and visual evoked potentials with no effect on morphological examinations, while the patient with 11778G>A mutation in mtND4 gene showed no functional, nor morphological recovery after one year of treatment. This study demonstrates that Idebenone, depending on the genetic profile of the disease, may be effective in functional improvement in patients with LHON.

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“…Mutations in the OPA1 gene affect mitochondrial fusion and leads to dominant optic neuropathy, the most common inherited optic neuropathy [ 131 ]. Mitochondrial DNA (mtDNA) can also harbor mutations that lead to disease, including Leber’s Hereditary Optic Neuropathy (LHON), which can occur due to a mutation in any of several mtDNA genes [ 132 , 133 ].…”

Section: Main Textmentioning

confidence: 99%

Solving neurodegeneration: common mechanisms and strategies for new treatments

Wareham

Liddelow²,

Temple

et al. 2022

Mol Neurodegeneration

135

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Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology or site of disease pathology. To address these mechanisms and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus Foundation, and the Melza M. and Frank Theodore Barr Foundation collaborated to bring together key opinion leaders and experts in the field of neurodegenerative disease for a virtual meeting titled “Solving Neurodegeneration”. This “think-tank” style meeting focused on uncovering common mechanistic roots of neurodegenerative disease and promising targets for new treatments, catalyzed by the goal of finding new treatments for glaucoma, the world’s leading cause of irreversible blindness and the common interest of the three hosting foundations. Glaucoma, which causes vision loss through degeneration of the optic nerve, likely shares early cellular and molecular events with other neurodegenerative diseases of the central nervous system. Here we discuss major areas of mechanistic overlap between neurodegenerative diseases of the central nervous system: neuroinflammation, bioenergetics and metabolism, genetic contributions, and neurovascular interactions. We summarize important discussion points with emphasis on the research areas that are most innovative and promising in the treatment of neurodegeneration yet require further development. The research that is highlighted provides unique opportunities for collaboration that will lead to efforts in preventing neurodegeneration and ultimately vision loss.

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Leber Hereditary Optic Neuropathy: Review of Treatment and Management

Cited by 46 publications

References 68 publications

Multi-mtDNA Variants May Be a Factor Contributing to Mitochondrial Function Variety in the Skin-Derived Fibroblasts of Leber's Hereditary Optic Neuropathy Patients

Multi-mtDNA Variants May Be a Factor Contributing to Mitochondrial Function Variety in the Skin-Derived Fibroblasts of Leber's Hereditary Optic Neuropathy Patients

Retinal morphological and functional response to Idebenone therapy in Leber hereditary optic neuropathy

Solving neurodegeneration: common mechanisms and strategies for new treatments

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