Isolated and syndromic genetic optic neuropathies: a review of genetic and phenotypic heterogeneity
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Nonsyndromic and syndromic hereditary optic neuropathies (HONs) encompass a variety of genetic illnesses that cause progressive optic nerve damage, resulting in considerable vision impairment. These disorders result from pathogenic variants in mitochondrial or nuclear DNA, impacting essential cellular processes like oxidative phosphorylation, mitochondrial dynamics, and neuroprotection. Advances in next-generation sequencing (NGS) have significantly improved the identification of genetic variations, enabling precise diagnoses and genotype–phenotype correlations. This review consolidates current knowledge regarding the classification, molecular pathogenesis, clinical manifestations, diagnostic methodologies, and emerging therapeutic strategies for HONs. The critical role of mitochondrial dysfunction in optic nerve degeneration highlights the necessity for multimodal therapeutic approaches. Recent clinical trials evaluating gene therapy for Leber hereditary optic neuropathy (LHON) and neuroprotective strategies in dominant optic atrophy (DOA) are discussed. Additionally, individualized therapeutic interventions, as demonstrated by recent case studies involving tailored gene therapies, are evaluated. The integration of molecular and imaging biomarkers in future personalized treatment strategies aims to enhance prognosis and therapeutic outcomes.
Date Issued
2025-04-20
Date Acceptance
2025-04-16
Citation
International Journal of Molecular Sciences, 2025, 26 (8)
ISSN
1661-6596
Publisher
MDPI AG
Journal / Book Title
International Journal of Molecular Sciences
Volume
26
Issue
8
Copyright Statement
©2025 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/40332750
PII: ijms26083892
Subjects
ATROPHY
Biochemistry & Molecular Biology
Chemistry
Chemistry, Multidisciplinary
COHERENCE TOMOGRAPHY
dominant optic atrophy (DOA)
FIBER LAYER EVALUATION
gene therapy
hereditary optic neuropathy
Leber hereditary optic neuropathy (LHON)
Life Sciences & Biomedicine
mitochondrial DNA
MITOCHONDRIAL HOMEOSTASIS
MUTATION
NERVE-FIBER
OPA1
optic atrophy
Physical Sciences
PREVALENCE
RETINAL GANGLION-CELLS
Science & Technology
wolfram syndrome
WOLFRAM-SYNDROME
Publication Status
Published
Coverage Spatial
Switzerland
Article Number
3892
Date Publish Online
2025-11-06