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Open Access 01-12-2016 | Review

A neurodegenerative perspective on mitochondrial optic neuropathies

Authors: Patrick Yu-Wai-Man, Marcela Votruba, Florence Burté, Chiara La Morgia, Piero Barboni, Valerio Carelli

Published in: Acta Neuropathologica | Issue 6/2016

Abstract

Mitochondrial optic neuropathies constitute an important cause of chronic visual morbidity and registrable blindness in both the paediatric and adult population. It is a genetically heterogeneous group of disorders caused by both mitochondrial DNA (mtDNA) mutations and a growing list of nuclear genetic defects that invariably affect a critical component of the mitochondrial machinery. The two classical paradigms are Leber hereditary optic neuropathy (LHON), which is a primary mtDNA disorder, and autosomal dominant optic atrophy (DOA) secondary to pathogenic mutations within the nuclear gene OPA1 that encodes for a mitochondrial inner membrane protein. The defining neuropathological feature is the preferential loss of retinal ganglion cells (RGCs) within the inner retina but, rather strikingly, the smaller calibre RGCs that constitute the papillomacular bundle are particularly vulnerable, whereas melanopsin-containing RGCs are relatively spared. Although the majority of patients with LHON and DOA will present with isolated optic nerve involvement, some individuals will also develop additional neurological complications pointing towards a greater vulnerability of the central nervous system (CNS) in susceptible mutation carriers. These so-called “plus” phenotypes are mechanistically important as they put the loss of RGCs within the broader perspective of neuronal loss and mitochondrial dysfunction, highlighting common pathways that could be modulated to halt progressive neurodegeneration in other related CNS disorders. The management of patients with mitochondrial optic neuropathies still remains largely supportive, but the development of effective disease-modifying treatments is now within tantalising reach helped by major advances in drug discovery and delivery, and targeted genetic manipulation.

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Title: A neurodegenerative perspective on mitochondrial optic neuropathies
Authors: Patrick Yu-Wai-Man
Marcela Votruba
Florence Burté
Chiara La Morgia
Piero Barboni
Valerio Carelli
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 6/2016
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-016-1625-2

At a glance: The STEP trials

Springer Medicine

A neurodegenerative perspective on mitochondrial optic neuropathies

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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