scholarly journals OPA1 Deficiency Associated with Increased Autophagy in Retinal Ganglion Cells in a Murine Model of Dominant Optic Atrophy

2009 ◽  
Vol 50 (6) ◽  
pp. 2567 ◽  
Author(s):  
Kathryn E. White ◽  
Vanessa J. Davies ◽  
Vanessa E. Hogan ◽  
Malgorzata J. Piechota ◽  
Philip P. Nichols ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Murine Model ◽  
Optic Atrophy ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Dominant Optic Atrophy

scholarly journals First submicroscopic inversion of the OPA1 gene identified in dominant optic atrophy – a case report

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Nicole Weisschuh ◽  
Pascale Mazzola ◽  
Tilman Heinrich ◽  
Tobias Haack ◽  
Bernd Wissinger ◽  
...  
Keyword(s):  
Optic Atrophy ◽  
Ganglion Cells ◽  
Visual Fields ◽  
Copy Number Variants ◽  
Retinal Ganglion ◽  
Single Nucleotide ◽  
Case Presentation ◽  
Dominant Optic Atrophy ◽  
Pathogenic Variants ◽  
Opa1 Gene

Abstract Background Dominant optic atrophy (DOA) is an inherited optic neuropathy that mainly affects visual acuity, central visual fields and color vision due to a progressive loss of retinal ganglion cells and their axons that form the optic nerve. Approximately 45–90% of affected individuals with DOA harbor pathogenic variants in the OPA1 gene. The mutation spectrum of OPA1 comprises nonsense, canonical and non-canonical splice site, frameshift and missense as well as copy number variants, but intragenic inversions have not been reported so far. Case presentation We report a 33-year-old male with characteristic clinical features of DOA. Whole-genome sequencing identified a structural variant of 2.4 kb comprising an inversion of 937 bp at the OPA1 locus. Fine mapping of the breakpoints to single nucleotide level revealed that the structural variation was an inversion flanked by two deletions. As this rearrangement inverts the entire first exon of OPA1, it was classified as likely pathogenic. Conclusions We report the first DOA case harboring an inversion in the OPA1 gene. Our study demonstrates that copy-neutral genomic rearrangements have to be considered as a possible cause of disease in DOA cases.

scholarly journals Acteoside inhibits autophagic apoptosis of retinal ganglion cells to rescue glaucoma‐induced optic atrophy

2019 ◽  
Vol 120 (8) ◽  
pp. 13133-13140 ◽  
Author(s):  
Qianbo Chen ◽  
Xiaoting Xi ◽  
Yong Zeng ◽  
Zhendan He ◽  
Jianfeng Zhao ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Optic Atrophy ◽  
Ganglion Cells ◽  
Retinal Ganglion

scholarly journals Wolfram syndrome: new pathophysiological insights and therapeutic strategies

2021 ◽  
Vol 2 ◽  
pp. 263300402110395
Author(s):  
Ratnakar Mishra ◽  
Benson S. Chen ◽  
Prachi Richa ◽  
Patrick Yu-Wai-Man
Keyword(s):  
Diabetes Mellitus ◽  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Optic Atrophy ◽  
Visual Loss ◽  
Ganglion Cells ◽  
Wolfram Syndrome ◽  
Retinal Ganglion ◽  
Wfs1 Gene ◽  
The Brain

Wolfram Syndrome (WS) is an ultra-rare, progressive neurodegenerative disease characterized by early-onset diabetes mellitus and irreversible loss of vision, secondary to optic nerve degeneration. Visual loss in WS is an important cause of registrable blindness in children and young adults and the pathological hallmark is the preferential loss of retinal ganglion cells within the inner retina. In addition to optic atrophy, affected individuals frequently develop variable combinations of neurological, endocrinological, and psychiatric complications. The majority of patients carry recessive mutations in the WFS1 (4p16.1) gene that encodes for a multimeric transmembrane protein, wolframin, embedded within the endoplasmic reticulum (ER). An increasingly recognised subgroup of patients harbor dominant WFS1 mutations that usually cause a milder phenotype, which can be limited to optic atrophy. Wolframin is a ubiquitous protein with high levels of expression in retinal, neuronal, and muscle tissues. It is a multifunctional protein that regulates a host of cellular functions, in particular the dynamic interaction with mitochondria at mitochondria-associated membranes. Wolframin has been implicated in several crucial cellular signaling pathways, including insulin signaling, calcium homeostasis, and the regulation of apoptosis and the ER stress response. There is currently no cure for WS; management remains largely supportive. This review will cover the clinical, genetic, and pathophysiological features of WS, with a specific focus on disease models and the molecular pathways that could serve as potential therapeutic targets. The current landscape of therapeutic options will also be discussed in the context of the latest evidence, including the pipeline for repurposed drugs and gene therapy. Plain language summary Wolfram syndrome – disease mechanisms and treatment options Wolfram syndrome (WS) is an ultra-rare genetic disease that causes diabetes mellitus and progressive loss of vision from early childhood. Vision is affected in WS because of damage to a specialized type of cells in the retina, known as retinal ganglion cells (RGCs), which converge at the back of the eye to form the optic nerve. The optic nerve is the fast-conducting cable that transmits visual information from the eye to the vision processing centers within the brain. As RGCs are lost, the optic nerve degenerates and it becomes pale in appearance (optic atrophy). Although diabetes mellitus and optic atrophy are the main features of WS, some patients can develop more severe problems because the brain and other organs, such as the kidneys and the bladder, are also affected. The majority of patients with WS carry spelling mistakes (mutations) in the WFS1 gene, which is located on the short arm of chromosome 4 (4p16.1). This gene is highly expressed in the eye and in the brain, and it encodes for a protein located within a compartment of the cell known as the endoplasmic reticulum. For reasons that still remain unclear, WFS1 mutations preferentially affect RGCs, accounting for the prominent visual loss in this genetic disorder. There is currently no effective treatment to halt or slow disease progression and management remains supportive, including the provision of visual aids and occupational rehabilitation. Research into WS has been limited by its relative rarity and the inability to get access to eye and brain tissues from affected patients. However, major advances in our understanding of this disease have been made recently by making use of more accessible cells from patients, such as skin cells (fibroblasts), or animal models, such as mice and zebrafish. This review summarizes the mechanisms by which WFS1 mutations affect cells, impairing their function and eventually leading to their premature loss. The possible treatment strategies to block these pathways are also discussed, with a particular focus on drug repurposing (i.e., using drugs that are already approved for other diseases) and gene therapy (i.e., replacing or repairing the defective WFS1 gene).

Calcium Signals Induced By Tonic Firing In Rat Retinal Ganglion Cells

2012 ◽  
Vol 3 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Kyril I. Kuznetsov ◽  
Vitaliy Yu. Maslov ◽  
Svetlana A. Fedulova ◽  
Nikolai S. Veselovsky
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Calcium Signals ◽  
Tonic Firing
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