Synthesis of Dideoxy-octonic Acid and Cyclic and Acyclic Derivatives Thereof
Org Lett. 2020 May 1;22(9):3373-3376. doi: 10.1021/acs.orglett.0c00842. Epub 2020 Apr 13. ABSTRACT Oxidative cleavage of N-acetyl-neuraminic acid (Neu5Ac, 1) leads to the open chain octonic acid (ADOA, 2), which under various conditions is transformed into an acyclic acid or ester or into a six- or five-membered octonic acid lactone and lactam, respectively. All reactions proceed […]
Comparison of Lamina Cribrosa Morphology in Normal Tension Glaucoma and Autosomal-Dominant Optic Atrophy
Invest Ophthalmol Vis Sci. 2020 May 11;61(5):9. doi: 10.1167/iovs.61.5.9. ABSTRACT PURPOSE: To compare lamina cribrosa (LC) morphology in patients with normal tension glaucoma (NTG) and autosomal-dominant optic atrophy (ADOA). METHODS: This cross-sectional study matched 24 patients diagnosed with ADOA (24 eyes) by age and retinal nerve fiber layer thickness with 48 patients diagnosed with NTG […]
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+/-) […]
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 […]
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 […]
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 […]
Mutation Screening of mtDNA Combined Targeted Exon Sequencing in a Cohort With Suspected Hereditary Optic Neuropathy
Transl Vis Sci Technol. 2020 Jul 8;9(8):11. doi: 10.1167/tvst.9.8.11. eCollection 2020 Jul. ABSTRACT PURPOSE: Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are the two commonest forms of hereditary optic neuropathy. The aim of this study was to comprehensively investigate the incidence and spectrum of mutations in patients with suspected hereditary optic […]
Genomics combined with a protein informatics platform to assess a novel pathogenic variant c.1024 A>G (p.K342E) in OPA1 in a patient with autosomal dominant optic atrophy
Ophthalmic Genet. 2020 Dec;41(6):563-569. doi: 10.1080/13816810.2020.1814344. Epub 2020 Sep 17. ABSTRACT BACKGROUND: Autosomal Dominant Optic Atrophy (ADOA) is caused by mutations in the Optic Atrophy 1 Gene which disrupts the OPA1 protein. This disruption affects the normal function of the protein; impairs fusion of the mitochondrial inner membrane; and prevents normal OPA1 protein degradation. These […]
Pathogenicity evaluation and the genotype-phenotype analysis of OPA1 variants
Mol Genet Genomics. 2021 Jul;296(4):845-862. doi: 10.1007/s00438-021-01783-0. Epub 2021 Apr 21. ABSTRACT Autosomal dominant optic atrophy (ADOA) is an important cause of irreversible visual impairment in children and adolescents. About 60-90% of ADOA is caused by the pathogenic variants of OPA1 gene. By evaluating the pathogenicity of OPA1 variants and summarizing the relationship between the […]
A Perspective on Accelerated Aging Caused by the Genetic Deficiency of the Metabolic Protein, OPA1
Front Neurol. 2021 Apr 13;12:641259. doi: 10.3389/fneur.2021.641259. eCollection 2021. ABSTRACT Autosomal Dominant Optic Atrophy (ADOA) is an ophthalmological condition associated primarily with mutations in the OPA1 gene. It has variable onset, sometimes juvenile, but in other patients, the disease does not manifest until adult middle age despite the presence of a pathological mutation. Thus, individuals […]