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Mitochondrial Optic Neuropathies

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Diagnosis and Management of Mitochondrial Disorders

Abstract

Optic atrophy is one the most frequent clinical manifestations of mitochondrial dysfunction, indicating how sensitive the retinal ganglion cells are to this metabolic insult. Typically mitochondrial optic neuropathies follow a common pattern, with small axons being more prone to degenerate due to their unfavorable metabolic setting. This leads to loss of papillomacular fibers characterized by central vision defect and prevalent temporal pallor at fundus examination. Leber’s hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA) are the two major clinical entities, and maternally inherited mitochondrial DNA mutations and heterozygous mutations in a nuclear gene, most frequently OPA1, are, respectively, found as diagnostic. The two disorders display also significant differences in terms of age of onset and natural history, with LHON being characterized by mostly young-adult age of onset with a subacute and rapidly evolving course, whereas DOA has infantile onset and slow progression. Our understanding of pathogenic mechanisms has dramatically increased in the last decades and has led to the approval of idebenone in LHON, so far (as of 2018) the only approved treatment in any mitochondrial disease. Other treatment approaches such as gene therapy are currently investigated. The extraordinary technological improvements now available, including reprogramming of stem cells from patients and the organoid technology, will possibly speed future research, casting hope for therapeutic success.

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Authors and Affiliations

  1. IRCCS Istituto di Scienze Neurologiche di Bologna, Bologna, Italy

    Valerio Carelli & Chiara La Morgia

  2. Dipartimento di Scienze Biomediche e Neuromotorie, Universita’ di Bologna, Bologna, Italy

    Valerio Carelli & Chiara La Morgia

  3. Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University of Munich, Munich, Germany

    Thomas Klopstock

  4. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany

    Thomas Klopstock

  5. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

    Thomas Klopstock

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    Thomas Klopstock

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Carelli, V., La Morgia, C., Klopstock, T. (2019). Mitochondrial Optic Neuropathies. In: Mancuso, M., Klopstock, T. (eds) Diagnosis and Management of Mitochondrial Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-05517-2_8

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