Zeppieri Marco, Gagliano Caterina, Di Maita Marco, Avitabile Alessandro, Gagliano Giuseppe, Dammino Edoardo, Tognetto Daniele, Cordeiro Maria Francesca, D'Esposito Fabiana
Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy.
Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy.
Int J Mol Sci. 2025 Apr 20;26(8):3892. doi: 10.3390/ijms26083892.
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.
非综合征性和综合征性遗传性视神经病变（HONs）包括多种导致进行性视神经损伤的遗传性疾病，从而造成严重的视力损害。这些疾病由线粒体或核DNA中的致病变异引起，影响氧化磷酸化、线粒体动力学和神经保护等重要细胞过程。下一代测序（NGS）技术的进步显著提高了基因变异的识别能力，有助于进行精确诊断和基因型-表型关联分析。本综述整合了关于HONs的分类、分子发病机制、临床表现、诊断方法及新兴治疗策略的现有知识。线粒体功能障碍在视神经变性中的关键作用凸显了多模式治疗方法的必要性。文中讨论了近期评估针对Leber遗传性视神经病变（LHON）的基因治疗和显性视神经萎缩（DOA）的神经保护策略的临床试验。此外，还评估了近期涉及定制基因治疗的病例研究中所展示的个体化治疗干预措施。分子和成像生物标志物在未来个性化治疗策略中的整合旨在改善预后和治疗效果。
