Research Topic

Hereditary Optic Neuropathies: A New Perspective

About this Research Topic

Hereditary optic neuropathies (HONs) are a heterogenous group of diseases largely caused by mitochondrial dysfunction, as a result of genetic defects in the mitochondrial and nuclear genomes. The two most common HONs are Leber’s Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), which are caused by mitochondrial DNA mutations and nuclear DNA mutations of the OPA1 gene, respectively. Recently, thanks to the availability of Next Generation Sequencing (NGS), the number of genes associated with isolated or syndromic HONs has rapidly expanded. The pathogenic mechanisms implicated in HONs recapitulate most of the key topics of neurodegeneration, widening their interest as a model of neurological disease. Excitingly, new therapeutic strategies including gene therapy are being developed for HONs.

The goal of this Research Topic is to provide a new perspective on recent advances in the genetic definition and clinical phenotyping, including electrophysiology, of HONs. We also aim to expand our understanding of the pathogenic mechanisms, and ultimately, the therapeutic options for HONs, with a particular focus on diagnosis and management. The recent increased availability of NGS has allowed for an exponential expansion in our understanding of the genetic basis of HONs. Furthermore, the widespread use of new technology, including OCT angiography, has allowed for earlier diagnosis and better phenotyping. Increased understanding of the natural history and therapeutic window of HONs, and the availability of inducible pluripotent stem cells (ipSCs) and organoids technology for studying pathogenic mechanisms and therapeutic options in HONs, will also be discussed. Finally, as we look to the future, the rapidly expanding use of artificial intelligence and its ability to change our clinical management paradigm will be explored.

Therefore, we welcome submissions of Original Research, Systematic Review, Review, Hypothesis and Theory, Mini Review and Brief Research Report manuscripts on the following subtopics:

- Historical perspective for HONs, from LHON to DOA and beyond;
- New genes associated with isolated OA involved in mitochondrial dynamics (AFG3L2, SPG7, OPA3, SLC25A46) and in mechanisms not related to mitochondrial dynamics (RTN4IP, TMEM126A, ACO2, SSBP1);
- Mitochondrial dysfunction as a common theme for HON including primary mitochondrial dysfunction (LHON and OPA1-related DOA) and possible secondary mitochondrial dysfunction (Wolfram’s syndrome);
- Recent advances in the knowledge of pathophysiology of HONs, including possible compensatory strategies in LHON (mitobiogenesis) and environmental factors as triggers;
- Surviving RGCs: the example of melanopsin RGCs;
- The use of the iPSCs/organoid models in HONs;
Main clinical findings - deep phenotyping in HONs;
- The role of electrophysiology in HONs;
- What visual recovery means in HONs: mechanisms to restore vision;
- Therapeutic options in HONs including gene therapy;
- Future directions towards personalized medicine in HONs.

Topic Editor Valerio Carelli received financial support from Stealth BioTherapeutics. The other Topic Editors declare no competing interests with regard to the Research Topic subject.


Keywords: optic nerve, mitochondria, LHON, DOA, therapy


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Hereditary optic neuropathies (HONs) are a heterogenous group of diseases largely caused by mitochondrial dysfunction, as a result of genetic defects in the mitochondrial and nuclear genomes. The two most common HONs are Leber’s Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), which are caused by mitochondrial DNA mutations and nuclear DNA mutations of the OPA1 gene, respectively. Recently, thanks to the availability of Next Generation Sequencing (NGS), the number of genes associated with isolated or syndromic HONs has rapidly expanded. The pathogenic mechanisms implicated in HONs recapitulate most of the key topics of neurodegeneration, widening their interest as a model of neurological disease. Excitingly, new therapeutic strategies including gene therapy are being developed for HONs.

The goal of this Research Topic is to provide a new perspective on recent advances in the genetic definition and clinical phenotyping, including electrophysiology, of HONs. We also aim to expand our understanding of the pathogenic mechanisms, and ultimately, the therapeutic options for HONs, with a particular focus on diagnosis and management. The recent increased availability of NGS has allowed for an exponential expansion in our understanding of the genetic basis of HONs. Furthermore, the widespread use of new technology, including OCT angiography, has allowed for earlier diagnosis and better phenotyping. Increased understanding of the natural history and therapeutic window of HONs, and the availability of inducible pluripotent stem cells (ipSCs) and organoids technology for studying pathogenic mechanisms and therapeutic options in HONs, will also be discussed. Finally, as we look to the future, the rapidly expanding use of artificial intelligence and its ability to change our clinical management paradigm will be explored.

Therefore, we welcome submissions of Original Research, Systematic Review, Review, Hypothesis and Theory, Mini Review and Brief Research Report manuscripts on the following subtopics:

- Historical perspective for HONs, from LHON to DOA and beyond;
- New genes associated with isolated OA involved in mitochondrial dynamics (AFG3L2, SPG7, OPA3, SLC25A46) and in mechanisms not related to mitochondrial dynamics (RTN4IP, TMEM126A, ACO2, SSBP1);
- Mitochondrial dysfunction as a common theme for HON including primary mitochondrial dysfunction (LHON and OPA1-related DOA) and possible secondary mitochondrial dysfunction (Wolfram’s syndrome);
- Recent advances in the knowledge of pathophysiology of HONs, including possible compensatory strategies in LHON (mitobiogenesis) and environmental factors as triggers;
- Surviving RGCs: the example of melanopsin RGCs;
- The use of the iPSCs/organoid models in HONs;
Main clinical findings - deep phenotyping in HONs;
- The role of electrophysiology in HONs;
- What visual recovery means in HONs: mechanisms to restore vision;
- Therapeutic options in HONs including gene therapy;
- Future directions towards personalized medicine in HONs.

Topic Editor Valerio Carelli received financial support from Stealth BioTherapeutics. The other Topic Editors declare no competing interests with regard to the Research Topic subject.


Keywords: optic nerve, mitochondria, LHON, DOA, therapy


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

07 July 2020 Abstract
10 November 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

07 July 2020 Abstract
10 November 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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