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Understanding the molecular basis and pathogenesis of hereditary optic neuropathies: towards improved diagnosis and management.
- Source :
-
The Lancet. Neurology [Lancet Neurol] 2023 Feb; Vol. 22 (2), pp. 172-188. Date of Electronic Publication: 2022 Sep 22. - Publication Year :
- 2023
-
Abstract
- Hereditary optic neuropathies result from defects in the human genome, both nuclear and mitochondrial. The two main and most recognised phenotypes are dominant optic atrophy and Leber hereditary optic neuropathy. Advances in modern molecular diagnosis have expanded our knowledge of genotypes and phenotypes of inherited disorders that affect the optic nerve, either alone or in combination, with various forms of neurological and systemic degeneration. A unifying feature in the pathophysiology of these disorders appears to involve mitochondrial dysfunction, suggesting that the retinal ganglion cells and their axons are especially susceptible to perturbations in mitochondrial homoeostasis. As we better understand the pathogenesis behind these genetic diseases, aetiologically targeted therapies are emerging and entering into clinical trials, including treatments aimed at halting the cascade of neurodegeneration, replacing or editing the defective genes or their protein products, and potentially regenerating damaged optic nerves, as well as preventing generational disease transmission.<br />Competing Interests: Declaration of interests NJN is a consultant for GenSight Biologics, Santhera/Chiesi, Stealth Biotherapeutics, and Neurophoenix; receives research support from GenSight Biologics and Santhera/Chiesi; is a participant in educational webinars sponsored by WebMD-Global Medscape and First Class; and is a medical-legal consultant in matters not related to this work. PY-W-M is a consultant for GenSight Biologics, Santhera/Chiesi, and PYC Therapeutics; receives research support from GenSight Biologics and Santhera/Chiesi; and is a participant in educational webinars sponsored by WebMD-Global Medscape and First Class. VB is a consultant for GenSight Biologics and Neurophoenix, and receives research support from GenSight Biologics and Santhera/Chiesi. VC is a consultant for GenSight Biologics, Santhera/Chiesi, and Stealth Biotherapeutics; receives research support from GenSight Biologics and Santhera/Chiesi; and is a participant in educational webinars sponsored by WebMD-Global Medscape and First Class.<br /> (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Subjects :
- Humans
Optic Nerve
Mitochondria genetics
Mitochondria metabolism
Mitochondria pathology
DNA, Mitochondrial genetics
Optic Nerve Diseases diagnosis
Optic Nerve Diseases genetics
Optic Nerve Diseases therapy
Optic Atrophy, Hereditary, Leber diagnosis
Optic Atrophy, Hereditary, Leber genetics
Optic Atrophy, Hereditary, Leber therapy
Optic Atrophy, Autosomal Dominant diagnosis
Optic Atrophy, Autosomal Dominant genetics
Optic Atrophy, Autosomal Dominant therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1474-4465
- Volume :
- 22
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Lancet. Neurology
- Publication Type :
- Academic Journal
- Accession number :
- 36155660
- Full Text :
- https://doi.org/10.1016/S1474-4422(22)00174-0