Britton John O T, Yu-Wai-Man Patrick, Chen Benson S
John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
Cambridge Eye Unit, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, United Kingdom.
Front Neurol. 2025 Jul 25;16:1609033. doi: 10.3389/fneur.2025.1609033. eCollection 2025.
Preferential degeneration of retinal ganglion cells (RGCs) is a defining feature of the inherited optic neuropathies (IONs), a group of monogenic eye diseases predominately comprising Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). Their pathogenesis is characterised by mitochondrial dysfunction, which causes loss of RGCs leading to irreversible vision loss. Although currently incurable, there are several emerging therapeutic avenues encompassing gene therapies, precision medicine strategies and neuroprotection. These are underscored by recent technological advances such as next-generation sequencing and improved disease modelling. In this review, we discuss these advances and the impact these will have on future diagnostic and treatment capabilities. We first focus on the clinical presentation and pathogenic mechanisms of LHON and DOA, followed by a discussion of emerging technology to facilitate diagnosis and treatment. We highlight the current unmet clinical demand of IONs, and the promise of current and future research developments.
视网膜神经节细胞(RGCs)的选择性退化是遗传性视神经病变(IONs)的一个决定性特征,这是一组单基因眼病,主要包括Leber遗传性视神经病变(LHON)和常染色体显性视神经萎缩(DOA)。它们的发病机制以线粒体功能障碍为特征,这会导致RGCs丧失,进而导致不可逆的视力丧失。尽管目前无法治愈,但有几种新兴的治疗途径,包括基因治疗、精准医学策略和神经保护。下一代测序和改进的疾病建模等最新技术进展突出了这些途径。在本综述中,我们讨论了这些进展以及它们对未来诊断和治疗能力的影响。我们首先关注LHON和DOA的临床表现和致病机制,然后讨论有助于诊断和治疗的新兴技术。我们强调了IONs目前未满足的临床需求,以及当前和未来研究进展的前景。