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Leber hereditary optic neuropathy—new insights and old challenges

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Abstract

Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA (mtDNA) disorder with the majority of patients harboring one of three primary mtDNA point mutations, namely, m.3460G>A (MTND1), m.11778G>A (MTND4), and m.14484T>C (MTND6). LHON is characterized by bilateral subacute loss of vision due to the preferential loss of retinal ganglion cells (RGCs) within the inner retina, resulting in optic nerve degeneration. This review describes the clinical features associated with mtDNA LHON mutations and recent insights gained into the disease mechanisms contributing to RGC loss in this mitochondrial disorder. Although treatment options remain limited, LHON research has now entered an active translational phase with ongoing clinical trials, including gene therapy to correct the underlying pathogenic mtDNA mutation.

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Acknowledgments

The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.

Funding

SSL is the recipient of the 2018 Roche Collaborative Research award from the ARVO Foundation for Eye Research. PYWM is supported by a Clinician Scientist Fellowship Award (G1002570) from the Medical Research Council (UK), and also receives funding from Fight for Sight (UK), the Isaac Newton Trust (UK), the Addenbrooke’s Charitable Trust, the National Eye Research Centre (UK), the UK National Institute of Health Research (NIHR) as part of the Rare Diseases Translational Research Collaboration, and the NIHR Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.

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  1. Srilekha Sundaramurthy and Ambika SelvaKumar contributed equally to this work.

Authors and Affiliations

  1. 1SN Oil and Natural Gas Corporation (ONGC) Department of Genetics & Molecular Biology, Vision Research Foundation, Chennai, India

    Srilekha Sundaramurthy & Sripriya Sarangapani

  2. Department of Neuro-Ophthalmology, Medical Research Foundation, Chennai, India

    Ambika SelvaKumar & Vidhya Dharani

  3. Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK

    Jared Ching & Patrick Yu-Wai-Man

  4. John Van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

    Jared Ching & Patrick Yu-Wai-Man

  5. NIHR Biomedical Research Centre, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK

    Patrick Yu-Wai-Man

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Sundaramurthy, S., SelvaKumar, A., Ching, J. et al. Leber hereditary optic neuropathy—new insights and old challenges. Graefes Arch Clin Exp Ophthalmol 259, 2461–2472 (2021). https://doi.org/10.1007/s00417-020-04993-1

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