Nanoengineered mitochondria enable ocular mitochondrial disease therapy via the replacement of dysfunctional mitochondria
Leber’s hereditary optic neuropathy (LHON) is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I, which is an important contributor to blindness among young adults across the globe. However, the disorder has no available cures, since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them. Herein, PARKIN mRNA-loaded nanoparticle (mNP)-engineered mitochondria (mNP-Mito) were designed to replace dysfunctional…
Idebenone Protects Photoreceptors Impaired by Oxidative Phosphorylation Disorder in Retinal Detachment
CONCLUSIONS: OXPHOS disorder leads to photoreceptor degeneration after RD, which can be alleviated by improving OXPHOS function.
Insights on the Genetic and Phenotypic Complexities of Optic Neuropathies
Background/Objectives: Optic neuropathies are a category of illnesses that ultimately cause damage to the optic nerve, leading to vision impairment and possible blindness. Disorders such as dominant optic atrophy (DOA), Leber hereditary optic neuropathy (LHON), and glaucoma demonstrate intricate genetic foundations and varied phenotypic manifestations. This narrative review study seeks to consolidate existing knowledge on the genetic and molecular mechanisms underlying ocular neuropathies,…
Visual Functions in Patients With Leber Hereditary Optic Neuropathy (LHON)
CONCLUSIONS: Face perception is strongly impaired in patients with LHON. In addition, although the selection and manipulation of real objects to execute a task are slowed, they can be performed efficiently using peripheral vision.
Risk Factors Associated With Leber Hereditary Optic Neuropathy due to Rare Mutations in Mitochondrial DNA-Encoded Respiratory Complex I Subunits
An in-depth analysis of susceptibility factors modifying the penetrance of rare Leber hereditary optic neuropathy-causing mutations in respiratory complex I genes encoded in mitochondrial deoxyribonucleic acid has not been performed. To bridge this gap, we conducted a review of the literature on rare mutations associated with LHON, selected those with substantial evidence of pathogenicity, and performed an in-depth analysis of the various pedigrees. Examining the influences that modify the…
Reprogramming patient-iPSC specific retinal organoids for deciphering epigenetic modifications of RNA methylation
CONCLUSION: These findings suggest that differential m6A modifications may play pivotal roles in the pathogenesis of retinal neurodegenerative diseases and affect the progression of the disease in affected individuals.
Clinical trials in Leber hereditary optic neuropathy: outcomes and opportunities
PURPOSE OF REVIEW: Leber hereditary optic neuropathy (LHON) is a mitochondrial DNA disease characterised by sequential bilateral vision loss due to loss of retinal ganglion cells. The purpose of this review is to provide an update on the results of recent clinical trials for LHON, focusing on studies of idebenone and lenadogene nolparvovec gene therapy.
Five-Year Outcomes of Lenadogene Nolparvovec Gene Therapy in Leber Hereditary Optic Neuropathy
CONCLUSIONS AND RELEVANCE: In this analysis of the RESTORE trial, follow-up of patients with LHON due to the MT-ND4 gene variant unilaterally treated with lenadogene nolparvovec demonstrated a sustained bilateral improvement in BCVA and a good safety profile up to 5 years after treatment. This evidence of persistent benefit over time is promising for the use of gene therapy in these patients.
DNAJC30 variants can also manifest phenotypically as Leigh/LHON overlap syndrome
No abstract
LNC-ing Genetics in Mitochondrial Disease
Primary mitochondrial disease (MD) is a group of rare genetic diseases reported to have a prevalence of 1:5000 and is currently without a cure. This group of diseases includes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), Leber’s hereditary optic neuropathy (LHON), Leigh syndrome (LS), Kearns-Sayre syndrome (KSS), and myoclonic epilepsy and ragged-red fiber disease (MERRF). Additionally, secondary mitochondrial…