Review
Ophthalmology
Guy Lenaers, Albert Neutzner, Yannick Le Dantec, Christoph Juschke, Ting Xiao, Sarah Decembrini, Sebastian Swirski, Sinja Kieninger, Cavit Agca, Ungsoo S. Kim, Pascal Reynier, Patrick Yu-Wai-Man, John Neidhardt, Bernd Wissinger
Summary: Dominant optic atrophy is an inherited mitochondrial disease characterized by specific degeneration of retinal ganglion cells, primarily caused by OPA1 mutations. OPA1 is crucial for mitochondrial function, and understanding RGC peculiarities is important for studying DOA pathophysiology.
PROGRESS IN RETINAL AND EYE RESEARCH
(2021)
Review
Clinical Neurology
Valentina Del Dotto, Valerio Carelli
Summary: The discovery of OPA1 mutations causing DOA in 2000 led to the rapid expansion of the field of mitochondrial dynamics and the exploration of complex pathways beyond its strict role in mitochondrial fusion. Translational mitochondrial medicine emphasizes the need for disease modeling at various levels, from yeast to animal models, to develop therapeutic strategies based on a thorough understanding of pathogenic mechanisms. This review provides an in-depth examination of the state of the art in these approaches.
FRONTIERS IN NEUROLOGY
(2021)
Article
Genetics & Heredity
Katherine A. Pohl, Xiangmei Zhang, Anh H. Pham, Jane W. Chan, Alfredo A. Sadun, Xian-Jie Yang
Summary: Dominant optic atrophy (DOA) is a genetic disease that results in the loss of retinal ganglion cells (RGCs) responsible for transmitting visual information from the retina to the brain. Mutations in the optic atrophy 1 (OPA1) gene, which encodes a mitochondrial protein, are the main cause of DOA. Recent advancements in stem cell biology have allowed the generation of RGCs from pluripotent stem cells (PSCs), providing a valuable tool to study DOA.
FRONTIERS IN GENETICS
(2023)
Review
Cell Biology
Nicole A. Muench, Sonia Patel, Margaret E. Maes, Ryan J. Donahue, Akihiro Ikeda, Robert W. Nickells
Summary: Mitochondrial function and dysfunction play important roles in neurodegeneration, especially in RGCs which are highly vulnerable due to their unique structure. Glaucoma represents a combination of events at the optic nerve head that increase metabolic stress on RGC axons, leading to axonal transport failure. Additionally, RGCs are sensitive to genetic mutations affecting mitochondrial dynamics and clearance, often resulting in optic neuropathy as the sole pathological defect.
Article
Biochemistry & Molecular Biology
Natalia Arruti, Patricia Rodriguez-Solana, Maria Nieves-Moreno, Marta Guerrero-Carretero, Angela del Pozo, Victoria E. F. Montano, Fernando Santos-Simarro, Emi Rikeros-Orozco, Luna Delgado-Mora, Elena Vallespin, Susana Noval
Summary: A clinical and genetic study was conducted to investigate the correlation between genotype and phenotype in pediatric patients with optic atrophy 1 (OPA1) mutations. Eleven children with confirmed OPA1 mutations were identified, with reduced visual acuity being the main complaint. Most patients had a positive family history of optic atrophy. The study found various mutations in the OPA1 gene, including one that has not been previously reported.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marta Zaninello, Konstantinos Palikaras, Aggeliki Sotiriou, Nektarios Tavernarakis, Luca Scorrano
Summary: Mitochondrial dysfunction and mitophagy are common characteristics of neurodegenerative diseases, and in ADOA, mitophagy depends on Ca2+-calcineurin-AMPK signaling cascade, providing insights into the pathogenesis of this disease.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Ophthalmology
Alexander M. Warwick, Howard M. Bomze, Luyu Wang, Mikael Klingeborn, Ying Hao, Sandra S. Stinnett, Sidney M. Gospe
Summary: Continuous hypoxia was found to have a significant neuroprotective effect on early retinal ganglion cell degeneration in mice with severe mitochondrial dysfunction. However, the complete rescue effect was not durable after a certain period of time. Hypoxia prevented gliosis but had limited effect on the accumulation of mononuclear phagocytic cells.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Cell Biology
Vittorio Porciatti, Tsung-Han Chou
Summary: This study introduces a framework to identify progressive and potentially reversible stages of RGC dysfunction leading to cell death in mouse models of glaucoma and other optic neuropathies. Mathematical equations are provided to describe state-transitions and modifiable parameters that can be used for hypothesis testing and fitting experimental PERG data. PERG dynamics are also utilized to differentiate phenotypic and altered RGC response dynamics, assess susceptibility to stressors, and evaluate reversible dysfunction with pharmacological treatment.
Article
Ophthalmology
Maria Kalogerou, Sotiris Ioannou, Panagiotis Kolovos, Ekatherine Prokopiou, Louiza Potamiti, Kyriacos Kyriacou, Michail Panagiotidis, Maria Ioannou, Eleni Fella, Elena Panayiotou Worth, Tassos Georgiou
Summary: The study evaluated the neuroprotective effects of ω-3 PUFAs in a mouse model of ADOA, showing that supplementation had protective effects on retinas through inhibition of inflammation and apoptosis. The findings also suggest that ω-3 PUFAs may not be involved in neuroprotection through inhibition of oxidative stress.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Anatomy & Morphology
Bum Jun Kim, Daryl A. Scott
Summary: RERE plays a crucial role in controlling apoptosis of retinal cells and its deficiency leads to retinal atrophy and optic nerve degeneration. RERE-deficient mice exhibit reduced number of retinal ganglion cells and progressive loss of retinal cells, particularly in the ganglion cell layer.
DEVELOPMENTAL DYNAMICS
(2021)
Review
Neurosciences
Elin L. Strachan, Delphi Mac White-Begg, John Crean, Alison L. Reynolds, Breandan N. Kennedy, Niamh C. O'Sullivan
Summary: Optic atrophy with autosomal inheritance is a progressive and irreversible vision loss disorder caused by mitochondrial dysfunction. Despite the lack of approved treatments and understanding of the mechanisms, further research is needed to develop therapies for this condition.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Clinical Neurology
Yuri Seo, Tae Young Kim, Dongju Won, Saeam Shin, Jong Rak Choi, Seung-Tae Lee, Byung Joo Lee, Hyun Taek Lim, Sueng-Han Han, Jinu Han
Summary: This study evaluated the clinical characteristics and causative genetic variants in autosomal optic atrophy using next-generation sequencing (NGS). The results showed that NGS had a diagnostic rate of 31.6% in patients with optic atrophy, with higher rates observed in patients with early onset. The major genetic causes were found in OPA1 and NR2F1 genes.
FRONTIERS IN NEUROLOGY
(2022)
Article
Cell & Tissue Engineering
Zixi Sun, Shijing Wu, Tian Zhu, Xing Wei, Xiaoxu Han, Xuan Zou, Ruifang Sui
Summary: The hiPSC line of DOA patient retains the disease-associated mutation, with normal karyotype, pluripotency, and differentiation capacity.
STEM CELL RESEARCH
(2022)
Article
Genetics & Heredity
Majida Charif, Arnaud Chevrollier, Naig Gueguen, Selma Kane, Celine Bris, David Goudenege, Valerie Desquiret-Dumas, Isabelle Meunier, Fanny Mochel, Luc Jeanjean, Fanny Varenne, Vincent Procaccio, Pascal Reynier, Dominique Bonneau, Patrizia Amati-Bonneau, Guy Lenaers
Summary: This study identifies heterozygous PMPCA variants as having a causative role in late-onset primary DOA. Functional assays suggest that these variants may affect the fusion-fission balance in mitochondria, leading to the degeneration of retinal ganglion cells.
Article
Neurosciences
Huseyin O. Taskin, Yuchuan Qiao, Valerie J. Sydnor, Matthew Cieslak, Edda B. Haggerty, Theodore D. Satterthwaite, Jessica I. W. Morgan, Yonggang Shi, Geoffrey K. Aguirre
Summary: There is considerable variation in the number of retinal ganglion cells (RGC) in the eye, which leads to variations in the optic tracts and subsequent structures along the visual pathway. Using diffusion MR analysis, the study investigated the correlation between RGC tissue volume and fiber density (FD) and cross section (FC) measurements from the optic tracts. The results showed that RGC endowment is correlated with FC but not with FD. Additionally, variations in each visual area were found to be correlated with variations in immediately adjacent visual structures.
Article
Multidisciplinary Sciences
Ingrid P. Meschede, Nicholas C. Ovenden, Miguel C. Seabra, Clare E. Futter, Marcelo Votruba, Michael E. Cheetham, Thomas Burgoyne
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Genetics & Heredity
Majida Charif, Arnaud Chevrollier, Naig Gueguen, Celine Bris, David Goudenege, Valerie Desquiret-Dumas, Stephanie Leruez, Estelle Colin, Audrey Meunier, Catherine Vignal, Vasily Smirnov, Sabine Defoort-Dhellemmes, Isabelle Drumare Bouvet, Cyril Goizet, Marcela Votruba, Neringa Jurkute, Patrick Yu-Wai-Man, Francesca Tagliavini, Leonardo Caporali, Chiara La Morgia, Valerio Carelli, Vincent Procaccio, Xavier Zanlonghi, Isabelle Meunier, Pascal Reynier, Dominique Bonneau, Patrizia Amati-Bonneau, Guy Lenaers
NEUROLOGY-GENETICS
(2020)
Article
Clinical Neurology
Claudia B. Catarino, Bettina von Livonius, Claudia Priglinger, Rudrani Banik, Selma Matloob, Madhura A. Tamhankar, Lorena Castillo, Christoph Friedburg, Christopher A. Halfpenny, John A. Lincoln, Ghislaine L. Traber, Goelge Acaroglu, Graeme C. M. Black, Carlos Doncel, Clare L. Fraser, Joanna Jakubaszko, Klara Landau, Stefan J. Langenegger, Francisco J. Munoz-Negrete, Nancy J. Newman, Joanna Poulton, Elisabetta Scoppettuolo, Prem Subramanian, Ahmed T. Toosy, Mariona Vidal, Andrea L. Vincent, Marcela Votruba, Marcin Zarowski, Adam Zermansky, Felice Lob, Guenther Rudolph, Oskars Mikazans, Magda Silva, Xavier Lloria, Guenther Metz, Thomas Klopstock
JOURNAL OF NEURO-OPHTHALMOLOGY
(2020)
Review
Nutrition & Dietetics
Gloria Cimaglia, Marcela Votruba, James E. Morgan, Helder Andre, Pete A. Williams
Meeting Abstract
Ophthalmology
Marcela Votruba, Lyndsey Butterworth, Catherine Feeney, Tracey Graves, Sarah Holmes, Amy Hunter, Jo Lowndes, Shamima Rahman, Jenny Sharpe, Rhys Thomas, Sheela Upadhaya, Lindsay Weaver, Russell Wheeler
ACTA OPHTHALMOLOGICA
(2021)
Article
Clinical Neurology
Irina Erchova, Shanshan Sun, Marcela Votruba
Summary: Autosomal Dominant Optic Atrophy (ADOA) is primarily caused by mutations in the OPA1 gene, with cellular pathology evident from birth in mutant cells. Early adaptation and cytoprotective responses lead to exhaustion of cellular reserves, particularly in neurons and skeletal muscle cells, resulting in premature cellular aging when natural defenses are overwhelmed.
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kathy Beirne, Thomas J. Freeman, Malgorzata Rozanowska, Marcela Votruba
Summary: The study utilized aged mice models to investigate the therapeutic potential of photobiomodulation (PBM) for retinal ganglion cell (RGC) degeneration. Results showed that in vivo 670 nm light pretreatment inhibited RGC dendropathy, indicating the potential of PBM as a treatment for diseases involving RGC degeneration. Additionally, the study revealed a potential molecular mechanism priming the retina to resist future oxidative insult, suggesting a promising direction for further research and treatment development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Dongjoon Kim, Marcela Votruba, Sayon Roy
Summary: Reduced level of Opa1 promotes apoptosis and retinal vascular lesions associated with diabetic retinopathy. Downregulation of Opa1 expression contributes to the development of retinal cell death and capillary damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
James R. Tribble, Amin Otmani, Shanshan Sun, Sevannah A. Ellis, Gloria Cimaglia, Rupali Vohra, Melissa Joe, Emma Lardner, Abinaya P. Venkataraman, Alberto Dominguez-Vicent, Eirini Kokkali, Seungsoo Rho, Gauti Johnnesson, Robert W. Burgess, Peter G. Fuerst, Rune Brautaset, Miriam Kolko, James E. Morgan, Jonathan G. Crowston, Marcela Votruba, Pete A. Williams
Summary: Research has shown that nicotinamide has neuroprotective effects on neurons affected in glaucoma, preventing metabolic disruption and increasing oxidative phosphorylation in cells to reduce firing frequency of neurons.
Meeting Abstract
Ophthalmology
Vincent Ng, Paul Cornes, Marcela Votruba
ACTA OPHTHALMOLOGICA
(2022)
Meeting Abstract
Ophthalmology
James McFadyen, Marcela Votruba, Michael Muenzberg, Paul Cornes
ACTA OPHTHALMOLOGICA
(2022)
Article
Endocrinology & Metabolism
Rhys H. Thomas, Amy Hunter, Lyndsey Butterworth, Catherine Feeney, Tracey D. Graves, Sarah Holmes, Pushpa Hossain, Jo Lowndes, Jenny Sharpe, Sheela Upadhyaya, Kristin N. Varhaug, Marcela Votruba, Russell Wheeler, Kristina Staley, Shamima Rahman
Summary: This article introduces a priority setting partnership project for primary mitochondrial disorders. By collecting research questions from patients, caregivers, and clinicians through online surveys and face-to-face workshops, the top 10 unanswered research questions were determined, including areas such as biological processes, new treatments, biomarkers, psychological support, and disease management.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Meeting Abstract
Ophthalmology
Marcela Votruba
ACTA OPHTHALMOLOGICA
(2022)
Meeting Abstract
Ophthalmology
Marcela Votruba
ACTA OPHTHALMOLOGICA
(2022)
Meeting Abstract
Ophthalmology
James McFadyen, Marcela Votruba, Michael Muenzberg, Paul Cornes
ACTA OPHTHALMOLOGICA
(2022)
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.