Insights on the genetic and phenotypic complexities of optic neuropathies
File(s)
Published version
Author(s)
D'Esposito, Fabiana
Zeppieri, Marco
Cordeiro, Maria Francesca
Capobianco, Matteo
Avitabile, Alessandro
Type
Journal Article
Abstract
Background/Objectives: Optic neuropathies are a category of illnesses that ultimately cause damage to the optic nerve, leading to vision impairment and possible blindness. Disorders such as dominant optic atrophy (DOA), Leber hereditary optic neuropathy (LHON), and glaucoma demonstrate intricate genetic foundations and varied phenotypic manifestations. This narrative review study seeks to consolidate existing knowledge on the genetic and molecular mechanisms underlying ocular neuropathies, examine genotype-phenotype correlations, and assess novel therapeutic options to improve diagnostic and treatment methodologies. Methods: A systematic literature review was performed in October 2024, utilizing PubMed, Medline, the Cochrane Library, and ClinicalTrials.gov. Search terms encompassed “optic neuropathy”, “genetic variants”, “LHON”, “DOA”, “glaucoma”, and “molecular therapies”. Studies were chosen according to established inclusion criteria, concentrating on the genetic and molecular dimensions of optic neuropathies and their therapeutic ramifications. Results: The results indicate that DOA and LHON are mostly associated with the mitochondrial dysfunction resulting from pathogenic variants in nuclear genes, mainly OPA1, and mitochondrial DNA (mtDNA) genes, respectively. Glaucoma, especially its intricate variants, is linked to variants in genes like MYOC, OPTN, and TBK1. Molecular mechanisms, such as oxidative stress and inflammatory modulation, are pivotal in disease progression. Innovative therapeutics, including gene therapy, RNA-based treatments, and antioxidants such as idebenone, exhibit promise for alleviating optic nerve damage and safeguarding vision. Conclusions: Genetic and molecular investigations have markedly enhanced our comprehension of ocular neuropathies. The amalgamation of genetic and phenotypic data is essential for customized medical strategies. Additional research is required to enhance therapeutic strategies and fill the gaps in our understanding of the underlying pathophysiology. This interdisciplinary approach shows potential for enhancing patient outcomes in ocular neuropathies.
Date Issued
2024-11-29
Date Acceptance
2024-11-28
Citation
Genes, 2024, 15 (12)
ISSN
2073-4425
Publisher
MDPI
Journal / Book Title
Genes
Volume
15
Issue
12
Copyright Statement
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39766826
PII: genes15121559
Subjects
COMMON
DISEASE
DNA METHYLATION
DOA
EXPRESSION
genetic variants
Genetics & Heredity
GENOME-WIDE ASSOCIATION
genotype-phenotype correlations
GLAUCOMA
glaucoma genetics
LHON
Life Sciences & Biomedicine
MECHANISMS
next-generation sequencing
optic neuropathy
personalized treatment
Science & Technology
SUSCEPTIBILITY LOCI
THERAPY
Publication Status
Published
Coverage Spatial
Switzerland
Article Number
1559
Date Publish Online
2024-11-29