Journal
CURRENT OPINION IN OPHTHALMOLOGY
Volume 28, Issue 5, Pages 403-409Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/ICU.0000000000000410
Keywords
gene therapy; Leber hereditary optic neuropathy; mitochondrial diseases; mitochondrial replacement; optical coherence tomography
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Funding
- Clinician Scientist Fellowship Award from the Medical Research Council (MRC, UK) [G1002570]
- Fight for Sight (UK)
- UK National Institute of Health Research (NIHR)
- NIHR Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust
- UCL Institute of Ophthalmology
- MRC [G0701386, G1002570] Funding Source: UKRI
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Purpose of reviewLeber 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 findingsLHON 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.SummaryLHON 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.
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