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Leber hereditary optic neuropathy: bridging the translational gap

Lookup NU author(s): Dr Patrick Yu Wai Man



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. PURPOSE OF REVIEW: Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA (mtDNA) genetic disorder in the population. We address the clinical evolution of the disease, the secondary etiological factors that could contribute to visual loss, and the challenging task of developing effective treatments. RECENT FINDINGS: LHON is characterized by a preclinical phase that reflects retinal ganglion cell (RGC) dysfunction before rapid visual deterioration ensues. Children can present atypically with slowly progressive visual loss or an insidious/subclinical onset that frequently results in considerable diagnostic delays. The LHON mtDNA mutation is not sufficient on its own to precipitate RGC loss and the current body of evidence supports a role for smoking and estrogen levels influencing disease conversion. Clinical trials are currently investigating the efficacy of adeno-associated viral vectors-based gene therapy approaches for patients carrying the m.11778G>A mutation. Mitochondrial replacement therapy is being developed as a reproductive option to prevent the maternal transmission of pathogenic mtDNA mutations. SUMMARY: LHON is phenotypically more heterogeneous than previously considered and a complex interplay of genetic, environmental and hormonal factors modulates the risk of a LHON carrier losing vision. Advances in disease modelling, drug screening and genetic engineering offer promising avenues for therapeutic breakthroughs in LHON.

Publication metadata

Author(s): Jurkute N, Yu-Wai-Man P

Publication type: Article

Publication status: Published

Journal: Current Opinion in Ophthalmology

Year: 2017

Volume: 28

Issue: 5

Pages: 403-409

Print publication date: 01/09/2017

Online publication date: 24/06/2017

Acceptance date: 02/04/2016

Date deposited: 13/10/2017

ISSN (print): 1040-8738

ISSN (electronic): 1531-7021

Publisher: Lippincott Williams and Wilkins


DOI: 10.1097/ICU.0000000000000410


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