Search results for "Optic Atrophy"
showing 4 items of 14 documents
Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy.
2012
Leber hereditary optic neuropathy (LHON) is a mitochondrially inherited form of visual dysfunction caused by mutations in several genes encoding subunits of the mitochondrial respiratory NADH-ubiquinone oxidoreductase complex (complex I). Development of gene therapies for LHON has been impeded by genetic heterogeneity and the need to deliver therapies to the mitochondria of retinal ganglion cells (RGCs), the cells primarily affected in LHON. The therapy under development entails intraocular injection of a nuclear yeast gene NADH-quinone oxidoreductase (NDI1) that encodes a single subunit complex I equivalent and as such is mutation independent. NDI1 is imported into mitochondria due to an e…
A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics
2011
Glutamate excitotoxicity leads to fragmented mitochondria in neurodegenerative diseases, mediated by nitric oxide and S-nitrosylation of dynamin-related protein 1, a mitochondrial outer membrane fission protein. Optic atrophy gene 1 (OPA1) is an inner membrane protein important for mitochondrial fusion. Autosomal dominant optic atrophy (ADOA), caused by mutations in OPA1, is a neurodegenerative disease affecting mainly retinal ganglion cells (RGCs). Here, we showed that OPA1 deficiency in an ADOA model influences N-methyl-D-aspartate (NMDA) receptor expression, which is involved in glutamate excitotoxicity and oxidative stress. Opa1enu/+mice show a slow progressive loss of RGCs, activation …
Su un caso di sindrome di Wolfram
2011
To aim of this paper was to offer a further contribution to the knowledge af the Wolfram Syndrome within the Italian population about hypotheses of its genetic trasmission and diagnostic problems.The study comprised the genetic investigation and the clinical ophthalmological examination of all the family members. Genetic investigation of family members showed the presence of a genetic disorder,consisting in a mutation of the gene wfs1, located on the short arm of chromosome 4, and which codifies for the protein Wolfranin. The gene wfs1 presents high penetrance and expression,since the mutation is recessive, it can only be clinicallly detected when it is present in the homozygous form. It sh…
Clinical and genetic characteristics of 21 Spanish patients with biallelic pathogenic SPG7 mutations.
2021
Spastic paraplegia type 7 (SPG7) is one of the most common hereditary spastic paraplegias. SPG7 mutations most often lead to spastic paraparesis (HSP) and/or hereditary cerebellar ataxia (HCA), frequently with mixed phenotypes. We sought to clinically and genetically characterize a Spanish cohort of SPG7 patients. Patients were recruited from our HCA and HSP cohorts. We identified twenty-one patients with biallelic pathogenic SPG7 mutations. Mean age at onset was 37.4 years (SD ± 14.3). The most frequent phenotype was spastic ataxia (57%), followed by pure spastic paraplegia (19%) and complex phenotypes (19%). Isolated patients presented with focal or multifocal dystonia, subclinical myopat…