New avenues for therapy in mitochondrial optic neuropathies

Ther Adv Rare Dis. 2021 Jul 19;2:26330040211029037. doi: 10.1177/26330040211029037. eCollection 2021 Jan-Dec. ABSTRACT Mitochondrial optic neuropathies are a group of optic nerve atrophies exemplified by the two commonest conditions in this group, autosomal dominant optic atrophy (ADOA) and Leber’s hereditary optic neuropathy (LHON). Their clinical features comprise reduced visual acuity, colour vision deficits, centro-caecal scotomas […]

In Vivo Efficacy and Safety Evaluations of Therapeutic Splicing Correction Using U1 snRNA in the Mouse Retina

Cells. 2023 Mar 21;12(6):955. doi: 10.3390/cells12060955. ABSTRACT Efficacy and safety considerations constitute essential steps during development of in vivo gene therapies. Herein, we evaluated efficacy and safety of splice factor-based treatments to correct mutation-induced splice defects in an Opa1 mutant mouse line. We applied adeno-associated viruses to the retina. The viruses transduced retinal cells with […]

Rescue of cell death and inflammation of a mouse model of complex 1-mediated vision loss by repurposed drug molecules

Hum Mol Genet. 2017 Dec 15;26(24):4929-4936. doi: 10.1093/hmg/ddx373. ABSTRACT Inherited mitochondrial optic neuropathies, such as Leber’s hereditary optic neuropathy (LHON) and Autosomal dominant optic atrophy (ADOA) are caused by mutant mitochondrial proteins that lead to defects in mitochondrial complex 1-driven ATP synthesis, and cause specific retinal ganglion cell (RGC) loss. Complex 1 defects also occur […]

Processing of OPA1 with a novel N-terminal mutation in patients with autosomal dominant optic atrophy: Escape from nonsense-mediated decay

PLoS One. 2017 Aug 25;12(8):e0183866. doi: 10.1371/journal.pone.0183866. eCollection 2017. ABSTRACT Autosomal Dominant Optic Atrophy (ADOA) is the most common dominantly inherited optic neuropathy. In the majority of patients it is caused by OPA1 mutations and those predicted to introduce a premature termination codon (PTC) are frequently detected. Transcripts containing PTC may be degraded by nonsense-mediated […]

A novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis

Sci Rep. 2017 Jul 18;7(1):5704. doi: 10.1038/s41598-017-05571-y. ABSTRACT Autosomal dominant optic atrophy (ADOA) is a dominantly inherited optic neuropathy, affecting the specific loss of retinal ganglion cells (RGCs). The majority of affected cases of ADOA are associated with mutations in OPA1 gene. Our previous investigation identified the c.1198C > G (p.P400A) mutation in the OPA1 […]

Pupillometric evaluation of the melanopsin containing retinal ganglion cells in mitochondrial and non-mitochondrial optic neuropathies

Mitochondrion. 2017 Sep;36:124-129. doi: 10.1016/j.mito.2017.07.003. Epub 2017 Jul 14. ABSTRACT In recent years, chromatic pupillometry is used in humans to evaluate the activity of melanopsin expressing intrinsic photosensitive retinal ganglion cells (ipRGCs). Blue light is used to stimulate the ipRGCs and red light activates the rod/cone photoreceptors. The late re-dilation phase of pupillary light reflex […]

Clinical and genetic features of eight Chinese autosomal-dominant optic atrophy pedigrees with six novel OPA1 pathogenic variants

Ophthalmic Genet. 2018 Oct;39(5):569-576. doi: 10.1080/13816810.2018.1466337. Epub 2018 Jun 28. ABSTRACT BACKGROUND: Autosomal-dominant optic atrophy (ADOA) is one of the most common types of inherited optic atrophy. We identify OPA1 pathogenic variants and assess the clinical features of a cohort of Chinese ADOA patients Materials and Methods: Detailed clinical evaluations were performed and genomic DNA […]

Hereditary Optic Neuropathies

Klin Monbl Augenheilkd. 2018 Jun;235(6):747-763. doi: 10.1055/a-0583-6290. Epub 2018 Feb 28. ABSTRACT Hereditary optic nerve disorders are rare. For ophthalmologists, Leber’s hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are of particular relevance. LHON and ADOA are diseases of the retinal ganglion cells and are caused by mitchochondrial dysfunction. LHON is based on […]