Review
Genetics & Heredity
Qingyue Ma, Ying Sun, Ke Lei, Wenjuan Luo
Summary: This article summarizes the recent research progress on LHON, aiming to identify the genetic pathogenesis and clinical treatment points.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Article
Biochemistry & Molecular Biology
Hui-Chen Cheng, Sheng-Chu Chi, Chiao-Ying Liang, Jenn-Yah Yu, An-Guor Wang
Summary: Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease caused by mitochondria DNA (mtDNA) mutation, with incomplete penetrance and male prevalence. Whole exome sequencing (WES) revealed that many mitochondria-related nuclear genes are involved in the penetrance of LHON, highlighting the potential of WES in identifying candidate genes in molecular genetics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Kanchalika Sathianvichitr, Benjaporn Sigkaman, Niphon Chirapapaisan, Poramaet Laowanapiban, Tanyatuth Padungkiatsagul, Supanut Apinyawasisuk, Juthamat Witthayawerasak, Wanicha Chuenkongkaew
Summary: This study is the first to investigate the characteristics and prognosis of Leber's hereditary optic neuropathy (LHON) patients in Southeast Asia. The study found that the most common mutation in Thai LHON patients is G11778A, followed by T14484C. Male gender, older age, and the G11778A mutation are associated with poor vision outcomes.
ANNALS OF MEDICINE
(2022)
Article
Ophthalmology
Giacomo Calzetti, Chiara La Morgia, Marco Cattaneo, Arturo Carta, Francesca Bosello, Giulia Amore, Michele Carbonelli, Maria Lucia Cascavilla, Stefano Gandolfi, Valerio Carelli, Leopold Schmetterer, Hendrik P. N. Scholl, Piero Barboni
Summary: This study aimed to evaluate optic disk perfusion and neural retinal structure in patients with subacute LHON and LHON carriers. The findings suggest that high blood flow at the optic disk during the early subacute stage may be the result of vasodilation as compensation to mitochondrial impairment caused by LHON. Additionally, optic disk perfusion measured by LSFG shows promise as a biomarker for LHON diagnosis and monitoring.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Mirko Baglivo, Alessia Nasca, Eleonora Lamantea, Stefano Vinci, Manuela Spagnolo, Silvia Marchet, Holger Prokisch, Alessia Catania, Costanza Lamperti, Daniele Ghezzi
Summary: Leber's hereditary optic neuropathy (LHON) is a disease that causes visual loss due to damage to the optical nerve. In this study, the respiratory parameters of LHON patients' fibroblasts were evaluated, revealing reduced respiration in untreated conditions and no significant improvement after idebenone supplementation. The responsiveness of cultured cells to idebenone treatment did not fully reflect in vivo data, indicating the need for further evaluation of cellular respiration as a potential biomarker for LHON prognosis and treatment response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Yi Wang, Li-Fan Hu, Peng-Fei Cui, Lian-Yu Qi, Lei Xing, Hu-Lin Jiang
Summary: Leber's hereditary optic neuropathy (LHON) is a rare inherited blindness caused by mutations in mitochondrial DNA. The traditional chemotherapeutic agent Idebenone only alleviates symptoms, and in situ mitochondrial gene therapy is challenging. A novel pathologically responsive mitochondrial gene delivery vector named TISUH has been developed, showing promising potential for LHON treatment by targeting diseased mitochondria and releasing functional genes for correcting genetic abnormalities.
ADVANCED MATERIALS
(2021)
Article
Biology
George Balta, Georgiana Cristache, Andreea Diana Barac, Nicoleta Anton, Ileana Ramona Barac
Summary: This study shares the experience in diagnosing and managing patients with Leber's hereditary optic neuropathy, demonstrating positive outcomes with long-term Idebenone use. The findings contradict previous medical literature, as the female patient showed favorable evolution despite delayed diagnosis.
Article
Neurosciences
Ming-ming Sun, Huan-fen Zhou, Qiao Sun, Hong-en Li, Hong-juan Liu, Hong-lu Song, Mo Yang, Da Teng, Shi-hui Wei, Quan-gang Xu
Summary: This study investigated the clinical and radiologic characteristics of Leber's hereditary optic neuropathy (LHON) associated with other diseases. LHON was found to be accompanied by multiple diseases, especially different subtypes of optic neuritis. Additionally, the study observed idiopathic orbital inflammatory syndrome (IOIS) and compression optic neuropathy in relation to LHON for the first time.
FRONTIERS IN HUMAN NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Samuel J. Spiegel, Alfredo A. Sadun
Summary: This review summarizes the management strategies and treatment principles for Leber's Hereditary Optic Neuropathy (LHON), including preventive recommendations, current medical and supportive treatments, and emerging evidence for future potential therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Branislav Rovcanin, Jasna Jancic, Jelena Pajic, Marija Rovcanin, Janko Samardzic, Vesna Djuric, Blazo Nikolic, Nikola Ivancevic, Ivana Novakovic, Vladimir Kostic
Summary: The study aimed to evaluate oxidative stress in LHON patients and healthy individuals by assessing biomarkers in plasma. High levels of oxidative stress were found in LHON patients, indicating a potential role in the pathophysiology of the disease.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2021)
Article
Clinical Neurology
Camille Peron, Alessandra Maresca, Andrea Cavaliere, Angelo Iannielli, Vania Broccoli, Valerio Carelli, Ivano Di Meo, Valeria Tiranti
Summary: LHON, the first maternally inherited disease associated with homoplasmic mtDNA mutations, leads to selective degeneration of retinal ganglion cells and primarily affects young males, despite mutations present in all tissues. The lack of appropriate models for investigating pathogenic mechanisms has hampered our understanding, but emerging in-vitro models offer hope for accelerating research and testing therapeutic strategies for translation into clinic.
FRONTIERS IN NEUROLOGY
(2021)
Article
Ophthalmology
Juanjuan Zhang, Yanchun Ji, Jie Chen, Man Xu, Guoping Wang, Xiaorui Ci, Bing Lin, Jun Q. Mo, Xiangtian Zhou, Min-Xin Guan
Summary: Our study highlights the crucial role of the m.3460G>A mutation in the pathogenesis of LHON, characterized by mitochondrial dysfunction and alterations in apoptosis and mitophagy.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Neuroimaging
Ling Wang, Yi Ji, Hao Ding, Qin Tian, Ke Fan, Dapeng Shi, Chunshui Yu, Wen Qin
Summary: The study used arterial spin labeling (ASL) to investigate abnormal cerebral blood flow (CBF) in patients with Leber's hereditary optic neuropathy (LHON) and its associations with disease duration and neuro-ophthalmological impairment. The results showed differences in brain regions of LHON patients, including the left sensorimotor and bilateral visual areas. LHON patients had lower CBF in the bilateral calcarine compared to healthy controls. Chronic LHON patients also showed lower CBF in the left middle frontal gyrus, sensorimotor cortex, and temporal-partial junction. Disease duration and neuro-ophthalmological impairments were found to affect the metabolism of non-visual areas.
BRAIN IMAGING AND BEHAVIOR
(2023)
Review
Medicine, General & Internal
Yi-Ping Yang, Shania Foustine, Yu-Jer Hsiao, En-Tung Tsai, Fu-Ting Tsai, Chia-Lin Wang, Yu-Ling Ko, Hsiao-Yun Tai, Yi-Ching Tsai, Chang-Hao Yang, Yun-Ju Fu, An-Guor Wang, Yueh Chien
Summary: In 2018, the prevalence of optic neuropathies was estimated to be 115 per 100,000 population. Leber's Hereditary Optic Neuropathy (LHON) is a hereditary mitochondrial disease first identified in 1871. It is associated with three mtDNA point mutations, namely G11778A, T14484, and G3460A, affecting NADH dehydrogenase subunits. The absence of NADH dehydrogenase due to the mutations leads to ATP production cessation, resulting in the generation of reactive oxygen species and apoptosis of retinal ganglion cells. Additionally, environmental factors such as smoking and alcohol consumption are considered risk factors for LHON. Gene therapy and human induced pluripotent stem cells (hiPSCs) have shown promise in LHON research.
JOURNAL OF THE CHINESE MEDICAL ASSOCIATION
(2023)
Article
Cell Biology
Jane W. Chan, William Sultan, Rustum Karanjia, Alfredo A. Sadun
Summary: In this study, the visual effects of pharmacologic intervention with 4-aminopyridine (4-AP) in chronic Leber's Hereditary Optic Neuropathy (LHON) patients were examined. The addition of 4-AP showed potential for visual recovery in some LHON patients, but was ineffective in others.
Article
Biophysics
Marco Barbieri, Philip K. Lee, Leonardo Brizi, Enrico Giampieri, Francesco Solera, Gastone Castellani, Brian A. Hargreaves, Claudia Testa, Raffaele Lodi, Daniel Remondini
Summary: Magnetic resonance fingerprinting (MRF) is a fast quantitative MRI method. This study proposes a deep learning approach using a fully connected network (FCN) for MRF and compares it with the traditional dictionary-based approach. The results show that the FCN approach outperforms the dictionary-based approach in terms of scalability capabilities. The study also explores optimal training procedures to improve accuracy and robustness to noise and undersampling artifacts.
NMR IN BIOMEDICINE
(2022)
Review
Medicine, General & Internal
Yuting Xie, Fulvio Zaccagna, Leonardo Rundo, Claudia Testa, Raffaele Agati, Raffaele Lodi, David Neil Manners, Caterina Tonon
Summary: This article provides a comprehensive review of studies using CNN architectures to classify brain tumors. The study found that performance varied widely depending on the classification problem and network choice. Due to inconsistencies in validation methods, performance metrics, and training data reporting, there is currently no clear best method choice. Few studies have focused on clinical usability.
Article
Critical Care Medicine
Laura Maugeri, Aleksandar Jankovski, Emil Malucelli, Fabio Mangini, Jean-Michel Vandeweerd, Jacques Gilloteaux, Kathleen De Swert, Francesco Brun, Ginevra Begani Provinciali, Mauro DiNuzzo, Alberto Mittone, Alberto Bravin, Giuseppe Gigli, Federico Giove, Alessia Cedola, Charles Nicaise, Michela Fratini
Summary: A non-invasive imaging technique capable of capturing neuronal loss, vascular damage, and tissue reorganization following spinal cord injury (SCI) is currently lacking. In this study, a multi-modal approach combining synchrotron X-ray phase-contrast tomography (SXPCT), histology, and correlative methods was developed to study neurovascular architecture in SCI. SXPCT was able to capture neuronal loss and blood-brain barrier breakdown, providing high-resolution three-dimensional imaging of cellular changes.
JOURNAL OF NEUROTRAUMA
(2023)
Article
Ophthalmology
Catherine Vignal-Clermont, Patrick Yu-Wai-Man, Nancy J. Newman, Valerio Carelli, Mark L. Moster, Valerie Biousse, Prem S. Subramanian, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Alfredo A. Sadun, Thomas Klopstock, Robert C. Sergott, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Magali Taiel, Michel Roux, Jose-Alain Sahel
Summary: This study evaluated the safety profile of Lenadogene nolparvovec in patients with Leber hereditary optic neuropathy. A total of 189 patients received intravitreal injections of a recombinant adeno-associated virus 2 vector encoding the ND4 gene. The results showed that Lenadogene nolparvovec had a good overall safety profile with excellent systemic tolerability, and there were no serious treatment-related adverse events.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Ophthalmology
Piero Barboni, Chiara La Morgia, Maria Lucia Cascavilla, Eun Hee Hong, Marco Battista, Anna Majander, Leonardo Caporali, Vincenzo Starace, Giulia Amore, Antonio Di Renzo, Michele Carbonelli, Paolo Nucci, Neringa Jurkute, Benson S. Chen, Roberta Panebianco, Anna Maria De Negri, Federico Sadun, Vincenzo Parisi, Francesco Bandello, Alfredo A. Sadun, Valerio Carelli, Patrick Yu-wai-man
Summary: The purpose of this study was to investigate the clinical and molecular genetic features of childhood-onset Leber hereditary optic neuropathy (LHON) and understand the factors influencing the visual outcome. The study found that children who developed LHON before the age of 9 had a better visual prognosis than those who developed it later. This study is of importance for understanding LHON.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Ophthalmology
Valerio Carelli, Nancy J. Newman, Patrick Yu-Wai-Man, Valerie Biousse, Mark L. Moster, Prem S. Subramanian, Catherine Vignal-Clermont, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Robert C. Sergott, Thomas Klopstock, Alfredo A. Sadun, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Jean Francois Girmens, Chiara La Morgia, Adam A. DeBusk, Neringa Jurkute, Claudia Priglinger, Rustum Karanjia, Constant Josse, Julie Salzmann, Francois Montestruc, Michel Roux, Magali Taiel, Jose-Alain Sahel, The Lhon Study Group
Summary: Lenadogene nolparvovec is a promising gene therapy for LHON patients with MT-ND4 mutation, showing sustained visual acuity improvement compared to natural history. Incorporation of data from the latest trial REFLECT indicates that bilateral injection may offer added benefits over unilateral injection.
OPHTHALMOLOGY AND THERAPY
(2023)
Article
Ophthalmology
Enrico Borrelli, Alessandro Berni, Maria Lucia Cascavilla, Costanza Barresi, Marco Battista, Giorgio Lari, Michele Reibaldi, Francesco Bandello, Piero Barboni
Summary: This retrospective study examined the relationship between demographics, clinical characteristics, and structural OCT findings and long-term visual outcomes in patients with LHON treated with idebenone therapy. The results showed that the thickness of GC-IPL in the macula was associated with final BCVA at 2 years in these patients.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Ophthalmology
Leonardo Mastropasqua, Piero Barboni, Giacomo Savini, Emanuela Aragona, Rossella D'Aloisio, Manuela Lanzini, Luca Agnifili, Alice Galzignato, Antonio Solimeo, Karl Anders Knutsson, Elisabeth M. Messmer
Summary: Refractive surgery is a common elective surgery, but it can lead to dry eye disease (DED). Pre-existing untreated DED is a risk factor for dry eye symptoms after surgery. Recommendations for managing ocular surface and DED before and after refractive surgery are described, including the use of lubricating eye drops, ointments, anti-inflammatory agents, lid hygiene, and Intense Pulsed Light (IPL) treatment for meibomian gland dysfunction.
EUROPEAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Francesca Rossi, Giovanna Picone, Concettina Cappadone, Andrea Sorrentino, Marta Columbaro, Giovanna Farruggia, Emilio Catelli, Giorgia Sciutto, Silvia Prati, Robert Oliete, Alice Pasini, Eva Pereiro, Stefano Iotti, Emil Malucelli
Summary: Osteosarcoma (OS), the most common primary malignant bone tumor, is associated with osteogenic differentiation dysfunctions. In this study, conventional and X-ray synchrotron-based techniques were used to characterize mineral depositions in a human OS cell line (SaOS-2) exposed to osteogenic cocktail. The results showed that a partial restoration of physiological biomineralization occurred at 10 days after treatment, along with a mitochondria-driven mechanism for calcium transportation in the cells. Interestingly, mitochondria morphology changed during differentiation, indicating a metabolic reprogramming of OS cells possibly linked to increased glycolysis contribution to energy metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lucia Merolle, Lorella Pascolo, Luisa Zupin, Pietro Parisse, Valentina Bonanni, Gianluca Gariani, Sasa Kenig, Diana E. Bedolla, Sergio Crovella, Giuseppe Ricci, Stefano Iotti, Emil Malucelli, George Kourousias, Alessandra Gianoncelli
Summary: Although X-ray fluorescence microscopy is widely used for single-cell analysis, sample preparation remains a major challenge. The information on sample treatment is inadequate and unclear, leading to wasted time and jeopardizing the success of the experiment. Various fixation methods have been described, but none have been systematically tested for synchrotron X-ray microscopy.
Letter
Clinical Neurology
Giovanni Rizzo, Patrizia Avoni, Vincenzo Donadio, Rocco Liguori
NEUROLOGICAL SCIENCES
(2023)
Article
Behavioral Sciences
Benedetta Tafuri, Marco Filardi, Maria Elisa Frisullo, Roberto De Blasi, Giovanni Rizzo, Salvatore Nigro, Giancarlo Logroscino
Summary: This study uses machine learning techniques to analyze structural MRI data of patients with primary psychiatric disorders (PPD) and helps clinicians accurately diagnose behavioral variant frontotemporal dementia (bvFTD). The results indicate that gray matter atrophy in temporal, frontal, and occipital brain regions may be an important feature of dementia in PPD patients.
BRAIN AND BEHAVIOR
(2023)
Article
Biochemistry & Molecular Biology
Sara Castiglioni, Laura Locatelli, Giorgia Fedele, Alessandra Cazzaniga, Emil Malucelli, Stefano Iotti, Jeanette A. Maier
Summary: The TRPM7 channel plays a role in magnesium transport and has been suggested as a marker of endothelial function. In this study, TRPM7-silenced HUVEC cells were generated to investigate its role further. TRPM7-silenced HUVEC cells maintained cellular organization, reduced reactive oxygen species production, and exhibited faster growth. Intracellular magnesium concentration remained unchanged, but differences in magnesium distribution and upregulation of MagT1 were observed in TRPM7-silenced HUVEC cells.
Article
Clinical Neurology
Matteo Tagliapietra, Alex Incensi, Moreno Ferrarini, Nazarena Mesiano, Alessandro Furia, Giovanni Rizzo, Rocco Liguori, Tiziana Cavallaro, Salvatore Monaco, Gian Maria Fabrizi, Vincenzo Donadio
Summary: Small fiber neuropathy is a common manifestation in RFC1 disease, with severe and widespread somatic denervation observed. Skin denervation may be an early feature of this disorder.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Nutrition & Dietetics
Simona Parisse, Alessandra Gianoncelli, Gloria Isani, Francesco Luigi Gambaro, Giulia Andreani, Emil Malucelli, Giuliana Aquilanti, Ilaria Carlomagno, Raffaella Carletti, Monica Mischitelli, Flaminia Ferri, Veronica Paterna, Quirino Lai, Gianluca Mennini, Fabio Melandro, Cira Di Gioia, Massimo Rossi, Stefano Iotti, Michela Fratini, Stefano Ginanni Corradini
Summary: This study aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. The results showed that patients with cirrhosis had lower hepatic magnesium content and higher percentage of TRPM7-positive hepatocytes. The increase in hepatic magnesium content and TRPM7 expression were associated with worsening of MELDNa score. These findings suggest that severity of hepatocyte injury and prognosis in cirrhosis are closely related to magnesium depletion and overexpression of TRPM7.