LHON

Leber hereditary optic neuropathy (LHON) is a maternally inherited, bilateral, sequential optic neuropathy that usually affects young males. LHON arises from a defect in complex I of the oxidative phosphorylation chain that generates increased reactive oxygen species and causes a decline in cellular ATP production. There exists no cure at present for LHON. Asymptomatic LHON mutation carriers show signs of increased mitochondrial biogenesis that may compensate for the compromise in complex I activity. Partial recovery in LHON is associated with a wider optic disc diameter and a younger age at disease onset, which may allow for greater mitochondrial bioenergetic capacity...

Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON...

Mitochondrial (mt)DNA mutations have been revealed to be associated with Leber's hereditary optic neuropathy (LHON). The present study conducted clinical, genetic and molecular evaluations of two Han Chinese families. A total of 4 (3 men and 1 female) out of 14 matrilineal relatives in the families exhibited visual impairment with variable severity and age of onset. The average age of onset of visual loss was 20.5 years old. Molecular analysis of the complete mitochondrial genome in these pedigrees demonstrated that the three primary mutations associated with LHON were not detected; however, the homoplasmic m...

Ichthyosis with confetti (IWC) is a severe congenital genodermatosis characterized by ichthyosiform erythroderma since birth and confetti-like spots of normal skin appearing in childhood as a results of revertant mosaicism. This disorder is caused by mutations in KRT10 or KRT1 genes. We report a 16-year-old boy who presented ichthyosiform erythroderma with severe desquamation since birth and gradually worsening psycho-neurological symptoms (mental retardation, ataxia, dystonia, hypoacusis). The patient conspicuously lacked typical confetti-like spots at the age of 16...

Dominant optic atrophy (DOA) and Leber hereditary optic neuropathy (LHON) are the two most common inherited optic neuropathies encountered in clinical practice. This review provides a summary of recent advances in the understanding of the clinical manifestations, current treatments, and ongoing clinical trials of these two optic neuropathies. Substantial progress has been made in the understanding of the clinical, genetic, and pathophysiological basis of DOA and LHON. Pathogenic OPA1 gene mutations in DOA and 3 primary mutations of mitochondrial DNA in LHON-induced mitochondrial dysfunction, which in turn leads to increased reactive oxygen species levels in mitochondria and possibly insufficient ATP production...

Optic neuropathies, such as glaucoma and Leber's hereditary optic neuropathy (LHON) lead to retinal ganglion cell (RGC) loss and therefore motivate the application of transplantation technique into disease therapy. However, it is a challenge to direct the transplanted optic nerve axons to the correct location of the retina. The use of appropriate scaffold can promote the proper axon growth. Recently, biocompatible materials have been integrated into the medical field, such as tissue engineering and reconstruction of damaged tissues or organs...

Purpose: Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease in which optic neuropathy is considered a key feature. Several other manifestations of LHON have been reported; however, only little is known of their incidence and the life expectancy in LHON patients. Methods: This study, based on Danish nationwide health registries, included 141 patients diagnosed with LHON and 297 unaffected family members in the maternal line. The incidence of comorbidities and mortality for patients with LHON and unaffected family members was compared with that in the general population...

Complex I (CI) deficiency is one of the most common defects in the OXPHOS system; it represents more than 30% cases of mitochondrial diseases. The group is characterized by clinical and genetic heterogeneity and comprise several nosological forms. The most prevalent phenotypes for CI are LHON and Leigh syndrome. In this study we have analyzed skin fibroblasts from 11 patients with mutations in mtDNA, which cause LHON or Leigh-like phenotypes: m.11778 G>A (n=3), m.3460 A>G (n=2), m.3635 G>A (n=1), m...

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No abstract text is available yet for this article.

Leber's Hereditary Optic Neuropathy (LHON) shares features with Multiple Sclerosis (MS). Both diseases develop optic lesions. Frequent secondary LHON mutations in MS patients may explain the optic damage. Here, we tested the hypothesis that secondary LHON mutations are associated with optic neuritis (ON) in MS patients. We recruited 56 MS subjects with ON and 47 MS subjects without ON. DNA was extracted by salting out, after sampling of peripheral blood from each participant. We completed Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis with appropriate primers and restriction endonucleases for seven secondary LHON mutations...

Purpose: Leber's hereditary optic neuropathy (LHON; OMIM 535000) is one of the most common maternally inherited mitochondrial disorders. Three mitochondrial DNA point mutations-m.3460G>A (MT-ND1), m.11778G>A (MT-ND4), and m.14484T>C (MT-ND6)-account for the majority of reported LHON cases. Only approximately 50% of males and approximately 10% of females carrying these mutations develop optic neuropathy and blindness. Additional factors, such as mtDNA/nuclear genetic background and environmental modifiers, are likely to contribute toward the observed incomplete penetrance and gender bias...

PURPOSE: Leber hereditary optic neuropathy (LHON) is a mitochondrial inherited disease characterized by bilateral vision problems, such as reduced visual acuity, dyschromatopsia, and central or centrocecal scotoma. Of these cases, 95% are caused by three mutations in mitochondrial DNA (mtDNA): m.G11778A, followed by m.T14484C and m.G3460A. The remaining 5% of cases of LHON are caused by rare mutations also present in mtDNA. Although conventional molecular tools for molecular screening of LHON are becoming popular, in most cases these tools are still expensive and time-consuming and are difficult to reproduce...

Leber inherited optic neuropathy (LHON) is characterized by subacute bilateral loss of central vision due to dysfunction and loss of retinal ganglion cells (RGCs). Comprehensive visual electrophysiological investigations (including pattern reversal visual evoked potentials, pattern electroretinography and the photopic negative response) performed on 13 patients with acute and chronic LHON indicate early impairment of RGC cell body function and severe axonal dysfunction. Temporal, spatial and chromatic psychophysical tests performed on 7 patients with acute LHON and 4 patients with chronic LHON suggest severe involvement or loss of the midget, parasol and bistratified RGCs associated with all three principal visual pathways...

Incomplete penetrance characterizes the two most frequent inherited optic neuropathies, Leber's Hereditary Optic Neuropathy (LHON) and dominant optic atrophy (DOA), due to genetic errors in the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA), respectively. For LHON, compelling evidence has accumulated on the complex interplay of mtDNA haplogroups and environmental interacting factors, whereas the nDNA remains essentially non informative. However, a compensatory mechanism of activated mitochondrial biogenesis and increased mtDNA copy number, possibly driven by a permissive nDNA background, is documented in LHON; when successful it maintains unaffected the mutation carriers, but in some individuals it might be hampered by tobacco smoking or other environmental factors, resulting in disease onset...

In recent years, chromatic pupillometry is used in humans to evaluate the activity of melanopsin expressing intrinsic photosensitive retinal ganglion cells (ipRGCs). Blue light is used to stimulate the ipRGCs and red light activates the rod/cone photoreceptors. The late re-dilation phase of pupillary light reflex is primarily driven by the ipRGCs. Optic neuropathies i.e. Leber hereditary optic neuropathy (LHON), autosomal dominant optic atrophy (ADOA), nonarteritic anterior ischemic optic neuropathy (NAION), glaucoma, optic neuritis and idiopathic intracranial hypertension (IIH) are among the diseases, which have been subject to pupillometric studies...

PURPOSE: To quantitatively analyze the optic nerve alterations in chronic Leber's hereditary optic neuropathy (LHON) using reduced field-of-view diffusion tensor imaging (rFOV-DTI) and evaluate the correlation of diffusion parameters with visual functional and peripapillary retinal nerve fiber layer (RNFL) thickness. METHODS: Twenty-five patients (50 affected optic nerves) with chronic LHON and 28 healthy controls (56 normal optic nerves) were enrolled. The rFOV-DTI was performed in the bilateral optic nerves for all the subjects...

Mitochondrial dysfunction is associated with neuroinflammation and neurodegeneration disease, but its role as a driver in these processes is uncertain. Understanding the pathogenesis of inherited mitochondrial disorders may help us to uncover mechanisms involved during acquired mitochondrial dysfunction. We review the mechanisms of mitochondrial dysfunction in Leber's hereditary optic neuropathy and multiple sclerosis and discuss shared clinical and molecular features in both conditions. Targeting mitochondrial pathways involved in inflammation or apoptosis may be a possible therapeutic approach in multiple sclerosis...

PURPOSE OF REVIEW: Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA (mtDNA) genetic disorder in the population. We address the clinical evolution of the disease, the secondary etiological factors that could contribute to visual loss, and the challenging task of developing effective treatments. RECENT FINDINGS: LHON is characterized by a preclinical phase that reflects retinal ganglion cell (RGC) dysfunction before rapid visual deterioration ensues...

PURPOSE: To determine the effects of AAV2(Y444,500,730F)-P1ND4v2 in patients with Leber hereditary optic neuropathy (LHON). DESIGN: Prospective open-label, unilateral single-dose, intravitreal injection of AAV2(Y444,500,730F)-P1ND4v2 per participant. PARTICIPANTS: Fourteen patients with visual loss and mutated G11778A mitochondrial DNA. METHODS: Intravitreal injection with the gene therapy vector AAV2(Y444,500,730F)-P1ND4v2 into 1 eye...