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+/-) […]
Omega-3 fatty acids promote neuroprotection, decreased apoptosis and reduced glial cell activation in the retina of a mouse model of OPA1-related autosomal dominant optic atrophy
Exp Eye Res. 2022 Feb;215:108901. doi: 10.1016/j.exer.2021.108901. Epub 2021 Dec 20. ABSTRACT The purpose of this study was to evaluate the neuroprotective effects of omega-3 polyunsaturated fatty acid (ω3-PUFA) supplementation in a mouse model of OPA1-associated autosomal dominant optic atrophy (ADOA). The blood level of arachidonic acid (AA) and eicosapentaenoic acid (EPA) served to adjust […]
Autosomal dominant optic atrophy: A novel treatment for OPA1 splice defects using U1 snRNA adaption
Mol Ther Nucleic Acids. 2021 Oct 21;26:1186-1197. doi: 10.1016/j.omtn.2021.10.019. eCollection 2021 Dec 3. ABSTRACT Autosomal dominant optic atrophy (ADOA) is frequently caused by mutations in the optic atrophy 1 (OPA1) gene, with haploinsufficiency being the major genetic pathomechanism. Almost 30% of the OPA1-associated cases suffer from splice defects. We identified a novel OPA1 mutation, c.1065+5G>A, […]
Induced Pluripotent Stem Cells for Inherited Optic Neuropathies-Disease Modeling and Therapeutic Development
J Neuroophthalmol. 2022 Mar 1;42(1):35-44. doi: 10.1097/WNO.0000000000001375. Epub 2021 Sep 30. ABSTRACT BACKGROUND: Inherited optic neuropathies (IONs) cause progressive irreversible visual loss in children and young adults. There are limited disease-modifying treatments, and most patients progress to become severely visually impaired, fulfilling the legal criteria for blind registration. The seminal discovery of the technique for […]
Red Light Irradiation In Vivo Upregulates DJ-1 in the Retinal Ganglion Cell Layer and Protects against Axotomy-Related Dendritic Pruning
Int J Mol Sci. 2021 Aug 4;22(16):8380. doi: 10.3390/ijms22168380. ABSTRACT Retinal ganglion cells (RGCs) undergo dendritic pruning in a variety of neurodegenerative diseases, including glaucoma and autosomal dominant optic atrophy (ADOA). Axotomising RGCs by severing the optic nerve generates an acute model of RGC dendropathy, which can be utilized to assess the therapeutic potential of […]
Associations between OPA1, MFN1, and MFN2 polymorphisms and primary open angle glaucoma in Polish participants of European ancestry
Ophthalmic Genet. 2022 Feb;43(1):42-47. doi: 10.1080/13816810.2021.1970197. Epub 2021 Aug 23. ABSTRACT BACKGROUND: Glaucomatous optic nerve damage is caused by selective death of retinal ganglion cells (RGCs). Another condition with underlying loss of RGCs is autosomal dominant optic atrophy (ADOA). Majority of ADOA patients have mutations in OPA1, gene responsible for mitochondrial fusion final steps. Clinical […]
Sustained intracellular calcium rise mediates neuronal mitophagy in models of autosomal dominant optic atrophy
Cell Death Differ. 2022 Jan;29(1):167-177. doi: 10.1038/s41418-021-00847-3. Epub 2021 Aug 13. ABSTRACT Mitochondrial dysfunction and mitophagy are often hallmarks of neurodegenerative diseases such as autosomal dominant optic atrophy (ADOA) caused by mutations in the key mitochondrial dynamics protein optic atrophy 1 (Opa1). However, the second messengers linking mitochondrial dysfunction to initiation of mitophagy remain poorly […]
In Vivo Imaging of the Schlemm’s Canal and the Response to Selective Laser Trabeculoplasty
Am J Ophthalmol. 2022 Feb;234:126-137. doi: 10.1016/j.ajo.2021.07.002. Epub 2021 Jul 18. ABSTRACT OBJECTIVE: To evaluate the presence of angle dysgenesis on ASOCT (anterior segment optical coherence tomography) (ADoA) as a predictive factor in determining outcomes of selective laser trabeculoplasty (SLT). DESIGN: A prospective clinical cohort study. SUBJECTS: Patients with juvenile-onset open-angle glaucoma (JOAG) without angle […]