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)
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
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)
Article
Multidisciplinary Sciences
Saba Shahin, Bin Lu, Yueqin Zhou, Hui Xu, Jason Chetsawang, Robert H. Baloh, Shaomei Wang
Summary: Charcot-Marie-Tooth disease type 2A (CMT2A) is the most common inherited peripheral axonal neuropathy with over 100 dominant mutations, including the R94Q mutation in the MFN2 gene. CMT2A is characterized by progressive motor and sensory loss, color vision defects, and progressive loss of visual acuity. Using a transgenic mouse model with the R94Q mutation, researchers found extensive vision loss and retinal degeneration, which were rescued by augmenting MFN1 and restoring mitochondrial homeostasis.
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
Clinical Neurology
Nancy J. Newman, Patrick Yu-Wai-Man, Valerio Biousse, Valerio Carelli
Summary: Hereditary optic neuropathies are caused by defects in the human genome, affecting both nuclear and mitochondrial genes. The most common phenotypes are dominant optic atrophy and Leber hereditary optic neuropathy. Recent advances in molecular diagnosis have provided a deeper understanding of the genotypes and phenotypes of these disorders, which involve degeneration of the optic nerve and other neurological and systemic complications. Mitochondrial dysfunction appears to play a crucial role in the pathophysiology of these diseases, leading to the vulnerability of retinal ganglion cells and their axons. Targeted therapies aimed at halting neurodegeneration, gene replacement or editing, regeneration of damaged optic nerves, and prevention of disease transmission across generations are currently being explored in clinical trials.
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
Immunology
Laura Petrikowski, Sabrina Reinehr, Steffen Haupeltshofer, Leonie Deppe, Florian Graz, Ingo Kleiter, H. Burkhard Dick, Ralf Gold, Simon Faissner, Stephanie C. Joachim
Summary: In this study, inflammation and degeneration of the visual system were investigated in a spontaneous encephalomyelitis animal model. The findings showed concurrent inflammatory and degenerative mechanisms in the retina and optic nerve, involving the complement system.
FRONTIERS IN IMMUNOLOGY
(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
Ophthalmology
Sandeep Kumar, Hariharasubramanian Ramakrishnan, Suresh Viswanathan, Abram Akopian, Stewart A. Bloomfield
Summary: The study revealed that damage to the inner retina in glaucoma leads to impairments in the outer retina. Protecting the inner retinal neurons can effectively prevent damage to the outer retina.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Ophthalmology
Annika Balraj, Cheryl Clarkson-Paredes, Robert H. Miller
Summary: The myelin sheath is essential for signal conduction in axons and its disruption can cause functional deficits. This study used a mouse model to induce selective demyelination in the optic nerve and found that it resulted in changes in retinal network organization and reduced density of retinal ganglion cells. These findings highlight the importance of myelination in maintaining neural connectivity.
EXPERIMENTAL EYE RESEARCH
(2023)
Letter
Clinical Neurology
Sylvie Gerber, Majida Charif, Arnaud Chevrollier, Tanguy Chaumette, Claire Angebault, Selma Kane, Aurelien Paris, Jennifer Alban, Melanie Quiles, Cecile Delettre, Dominique Bonneau, Vincent Procaccio, Patrizia Amati-Bonneau, Pascal Reynier, Stephanie Leruez, Raphael Calmon, Nathalie Boddaert, Benoit Funalot, Marlene Rio, Didier Bouccara, Isabelle Meunier, Hiromi Sesaki, Josseline Kaplan, Christian P. Hamel, Jean-Michel Rozet, Guy Lenaers
Article
Genetics & Heredity
Lisbeth Tranebjaerg, Nicola Strenzke, Sture Lindholm, Nanna D. Rendtorff, Hanne Poulsen, Himanshu Khandelia, Wojciech Kopec, Troels J. Brunnich Lyngbye, Christian Hamel, Cecile Delettre, Beatrice Bocquet, Michael Bille, Hanne H. Owen, Toke Bek, Hanne Jensen, Karen Ostergaard, Claes Moller, Linda Luxon, Lucinda Carr, Louise Wilson, Kaukab Rajput, Tony Sirimanna, Katherine Harrop-Griffiths, Shamima Rahman, Barbara Vona, Julia Doll, Thomas Haaf, Oliver Bartsch, Hendrik Rosewich, Tobias Moser, Maria Bitner-Glindzicz
Correction
Genetics & Heredity
Lisbeth Tranebjaerg, Nicola Strenzke, Sture Lindholm, Nanna D. Rendtorff, Hanne Poulsen, Himanshu Khandelia, Wojciech Kopec, Troels J. Brunnich Lyngbye, Christian Hamel, Cecile Delettre, Beatrice Bocquet, Michael Bille, Hanne H. Owen, Toke Bek, Hanne Jensen, Karen Ostergaard, Claes Moller, Linda Luxon, Lucinda Carr, Louise Wilson, Kaukab Rajput, Tony Sirimanna, Katherine Harrop-Griffiths, Shamima Rahman, Barbara Vona, Julia Doll, Thomas Haaf, Oliver Bartsch, Hendrik Rosewich, Tobias Moser, Maria Bitner-Glindzicz
Review
Cell Biology
Benjamin Delprat, Tangui Maurice, Cecile Delettre
CELL DEATH & DISEASE
(2018)
Article
Multidisciplinary Sciences
Abrar Ul Haq Khan, Nerea Allende-Vega, Delphine Gitenay, Johan Garaude, Dang-NghiemVo, Sana Belkhala, Sabine Gerbal-Chaloin, Claire Gondeau, Martine Daujat-Chavanieu, Cecile Delettre, Stefania Orecchioni, Giovanna Talarico, Francesco Bertolini, Alberto Anel, Jose M. Cuezva, Jose A. Enriquez, Guillaume Cartron, Charles-Henri Lecellier, Javier Hernandez, Martin Villalba
SCIENTIFIC REPORTS
(2018)
Article
Biochemistry & Molecular Biology
Claire Angebault, Jeremy Fauconnier, Simone Patergnani, Jennifer Rieusset, Alberto Danese, Corentin A. Affortit, Jolanta Jagodzinska, Camille Megy, Melanie Quiles, Chantal Cazevieille, Julia Korchagina, Delphine Bonnet-Wersinger, Dan Milea, Christian Hamel, Paolo Pinton, Marc Thiry, Alain Lacampagne, Benjamin Delprat, Cecile Delettre
Article
Clinical Neurology
Agathe Roubertie, Majida Charif, Pierre Meyer, Gael Manes, Isabelle Meunier, Guillaume Taieb, Raul Junta Morales, Agnes Guichet, Cecile Delettre, Emmanuelle Sarzi, Nicolas Leboucq, Francois Rivier, Guy Lenaers
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2019)
Article
Medicine, Research & Experimental
Camille Piro-Megy, Emmanuelle Sarzi, Aleix Tarres-Sole, Marie Pequignot, Fenna Hensen, Melanie Quiles, Gael Manes, Arka Chakraborty, Audrey Senechal, Beatrice Bocquet, Chantal Cazevieille, Agathe Roubertie, Agnes Muller, Majida Charif, David Goudenege, Guy Lenaers, Helmut Wilhelm, Ulrich Kellner, Nicole Weisschuh, Bernd Wissinger, Xavier Zanlonghi, Christian Hamel, Johannes N. Spelbrink, Maria Sola, Cecile Delettre
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Cell Biology
Naig Gueguen, Julie Piarroux, Emmanuelle Sarzi, Mehdi Benkirane, Gael Manes, Cecile Delettre, Pascal Amedro, Nicolas Leboucq, Michel Koenig, Pierre Meyer, Isabelle Meunier, Pascal Reynier, Guy Lenaers, Agathe Roubertie
Summary: Biallelic pathogenic variants in ACAD9 lead to childhood-onset optic and peripheral neuropathy without cardiac involvement, with significant improvement in long-distance visual acuity and rescue of CI activity demonstrated with riboflavin treatment.
Article
Medicine, Research & Experimental
Benoit Gautier, Lena Meneux, Nadege Feret, Christine Audrain, Laetitia Hudecek, Alison Kuony, Audrey Bourdon, Caroline Le Guiner, Veronique Blouin, Cecile Delettre, Frederic Michon
Summary: Corneal blindness is a major cause of global blindness. Current research proposes the use of the lacrimal gland as a bioreactor to produce and secrete specific factors that support corneal physiology, aiming to address corneal blindness caused by tear film composition defects.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)