Validating the RedMIT/GFP-LC3 Mouse Model by Studying Mitophagy in Autosomal Dominant Optic Atrophy Due to the OPA1Q285STOP Mutation
Front Cell Dev Biol. 2018 Sep 19;6:103. doi: 10.3389/fcell.2018.00103. eCollection 2018. ABSTRACT Background: Autosomal dominant optic atrophy (ADOA) is usually caused by mutations in the essential gene, OPA1. This encodes a ubiquitous protein involved in mitochondrial dynamics, hence tissue specificity is not understood. Dysregulated mitophagy (mitochondria recycling) is implicated in ADOA, being increased in OPA1 […]
Genetic analysis in a cohort of patients with hereditary optic neuropathies in Southwest of China
Mitochondrion. 2019 May;46:327-333. doi: 10.1016/j.mito.2018.09.002. Epub 2018 Sep 7. ABSTRACT We report the results of molecular screening in 121 patients with suspected hereditary optic neuropathies. The 34 primary and 9 secondary LHON mutations were screened in all the patients. In the familial cases, OPA1 was also tested when negative finding for the mtDNA mutations screening. […]
Autosomal dominant optic atrophy plus due to the novel OPA1 variant c.1463G>C
Metab Brain Dis. 2019 Aug;34(4):1023-1027. doi: 10.1007/s11011-019-00425-0. Epub 2019 Jun 1. ABSTRACT OPA1 variants most frequently manifest phenotypically with pure autosomal dominant optic atrophy (ADOA) or with ADOA plus. The most frequent abnormalities in ADOA plus in addition to the optic nerve affection include hypoacusis, migraine, myopathy, and neuropathy. Hypertelorism and atrophy of the acoustic […]
Metabolic stroke in a patient with bi-allelic OPA1 mutations
Metab Brain Dis. 2019 Aug;34(4):1043-1048. doi: 10.1007/s11011-019-00415-2. Epub 2019 Apr 10. ABSTRACT OPA1 related disorders include: classic autosomal dominant optic atrophy syndrome (ADOA), ADOA plus syndrome and a bi-allelic OPA1 complex neurological disorder. We describe metabolic stroke in a patient with bi-allelic OPA1 mutations. A twelve-year old girl presented with a complex neurological disorder that […]
Peripapillary and macular morpho-vascular changes in patients with genetic or clinical diagnosis of autosomal dominant optic atrophy: a case-control study
Graefes Arch Clin Exp Ophthalmol. 2019 May;257(5):1019-1027. doi: 10.1007/s00417-019-04267-5. Epub 2019 Feb 24. ABSTRACT PURPOSE: To evaluate the macular and peripapillary morpho-vascular changes in ADOA, using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: Prospectively defined, cross-sectional case-control study. Consecutive patients with a genetic or clinical diagnosis of ADOA along with age- and sex-matched […]
Genetic Causes and Genetic Diagnostic Testing of Inherited Optic Atrophies
Klin Monbl Augenheilkd. 2018 Nov;235(11):1235-1241. doi: 10.1055/a-0759-2094. Epub 2018 Nov 20. ABSTRACT Hereditary optic atrophies are a heterogeneous group of rare degenerative disease affecting the retinal ganglion cells and their axons which form the optic nerve. With an estimated prevalence of 1 : 10 000 to 1 : 20 000, hereditary optic atrophies in their […]
Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy
Nat Commun. 2020 Aug 12;11(1):4029. doi: 10.1038/s41467-020-17821-1. ABSTRACT In autosomal dominant optic atrophy (ADOA), caused by mutations in the mitochondrial cristae biogenesis and fusion protein optic atrophy 1 (Opa1), retinal ganglion cell (RGC) dysfunction and visual loss occur by unknown mechanisms. Here, we show a role for autophagy in ADOA pathogenesis. In RGCs expressing mutated […]
Serum NT/CT SIRT1 ratio reflects early osteoarthritis and chondrosenescence
Ann Rheum Dis. 2020 Oct;79(10):1370-1380. doi: 10.1136/annrheumdis-2020-217072. Epub 2020 Jul 14. ABSTRACT OBJECTIVE: Previous work has established that the deacetylase sirtuin-1 (SIRT1) is cleaved by cathepsin B in chondrocytes subjected to proinflammatory stress, yielding a stable but inactive N-terminal (NT) polypeptide (75SIRT1) and a C-terminal (CT) fragment. The present work examined if chondrocyte-derived NT-SIRT1 is […]
A novel AFG3L2 mutation close to AAA domain leads to aberrant OMA1 and OPA1 processing in a family with optic atrophy
Acta Neuropathol Commun. 2020 Jun 29;8(1):93. doi: 10.1186/s40478-020-00975-w. ABSTRACT Autosomal dominant optic atrophy (ADOA) is a neuro-ophthalmic condition characterized by bilateral degeneration of the optic nerves. Although heterozygous mutations in OPA1 represent the most common genetic cause of ADOA, a significant number of cases remain undiagnosed.Here, we describe a family with a strong ADOA history […]
Opa1 Deficiency Leads to Diminished Mitochondrial Bioenergetics With Compensatory Increased Mitochondrial Motility
Invest Ophthalmol Vis Sci. 2020 Jun 3;61(6):42. doi: 10.1167/iovs.61.6.42. ABSTRACT PURPOSE: Retinal ganglion cells (RGCs) are susceptible to mitochondrial deficits and also the major cell type affected in patients with mutations in the OPA1 gene in autosomal dominant optic atrophy (ADOA). Here, we characterized mitochondria in RGCs in vitro from a heterozygous B6; C3-Opa1Q285STOP (Opa1+/-) […]