PDF(Pubmed)
Abstract：
More than 30 years after discovering Leber\'s hereditary optic neuropathy (LHON) as the first maternally inherited disease associated with homoplasmic mtDNA mutations, we still struggle to achieve effective therapies. LHON is characterized by selective degeneration of retinal ganglion cells (RGCs) and is the most frequent mitochondrial disease, which leads young people to blindness, in particular males. Despite that causative mutations are present in all tissues, only a specific cell type is affected. Our deep understanding of the pathogenic mechanisms in LHON is hampered by the lack of appropriate models since investigations have been traditionally performed in non-neuronal cells. Effective in-vitro models of LHON are now emerging, casting promise to speed our understanding of pathophysiology and test therapeutic strategies to accelerate translation into clinic. We here review the potentials of these new models and their impact on the future of LHON patients.
摘要：
在发现Leber的遗传性视神经病变（LHON）作为第一个与同质mtDNA突变相关的母系遗传性疾病超过30年后，我们仍在努力争取有效的治疗方法。LHON的特征是视网膜神经节细胞（RGCs）的选择性变性，是最常见的线粒体疾病，导致年轻人失明，尤其是男性。尽管致病突变存在于所有组织中,只有特定的细胞类型受到影响。由于传统上在非神经元细胞中进行研究，因此缺乏适当的模型阻碍了我们对LHON致病机制的深刻理解。LHON的有效体外模型正在出现，铸造有望加快我们对病理生理学的理解，并测试治疗策略，以加速转化为临床。我们在这里回顾这些新模型的潜力及其对LHON患者未来的影响。
