OPA1 mutation affects autophagy and triggers senescence in autosomal dominant optic atrophy plus fibroblasts

Hum Mol Genet. 2024 Jan 27:ddae008. doi: 10.1093/hmg/ddae008. Online ahead of print. ABSTRACT In several cases of mitochondrial diseases, the underlying genetic and bioenergetic causes of reduced oxidative phosphorylation (OxPhos) in mitochondrial dysfunction are well understood. However, there is still limited knowledge about the specific cellular outcomes and factors involved for each gene and mutation, […]

Predicting lost to follow-up status using an adolescent HIV psychosocial attrition risk assessment tool: Results from a mixed methods prospective cohort study in Uganda

J Acquir Immune Defic Syndr. 2024 Jan 2. doi: 10.1097/QAI.0000000000003381. Online ahead of print. ABSTRACT BACKGROUND: Low retention in care for adolescents living with HIV (ALHIV) has been a key driver of sub-optimal viral load suppression rates in Uganda. The objective of the study was to develop a psychosocial risk assessment tool and evaluate its […]

In vivo identification of angle dysgenesis and its relation to genetic markers associated with glaucoma using artificial intelligence

Indian J Ophthalmol. 2023 Dec 26. doi: 10.4103/IJO.IJO_1456_23. Online ahead of print. ABSTRACT PURPOSE: To predict the presence of angle dysgenesis on anterior-segment optical coherence tomography (ADoA) by using deep learning (DL) and to correlate ADoA with mutations in known glaucoma genes. PARTICIPANTS: In total, 800 high-definition anterior-segment optical coherence tomography (AS-OCT) images were included, […]

Human retinal organoids with an OPA1 mutation are defective in retinal ganglion cell differentiation and function

Stem Cell Reports. 2023 Nov 27:S2213-6711(23)00453-8. doi: 10.1016/j.stemcr.2023.11.004. Online ahead of print. ABSTRACT Autosomal dominant optic atrophy (ADOA), mostly caused by heterozygous OPA1 mutations and characterized by retinal ganglion cell (RGC) loss and optic nerve degeneration, is one of the most common types of inherited optic neuropathies. Previous work using a two-dimensional (2D) differentiation model […]

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 […]