University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States of America.
University of the Incarnate Word School of Medicine, 7615 Kennedy Hill Drive, San Antonio, TX 78235, United States of America.
Biochim Biophys Acta Mol Basis Dis. 2020 Jun 1;1866(6):165743. doi: 10.1016/j.bbadis.2020.165743. Epub 2020 Feb 24.
Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease mainly affecting retinal ganglion cells (RGCs). The pathogenesis of LHON remains ill-characterized due to a historic lack of effective disease models. Promising models have recently begun to emerge; however, less effective models remain popular. Many such models represent LHON using non-neuronal cells or assume that mutant mtDNA alone is sufficient to model the disease. This is problematic because context-specific factors play a significant role in LHON pathogenesis, as the mtDNA mutation itself is necessary but not sufficient to cause LHON. Effective models of LHON should be capable of demonstrating processes that distinguish healthy carrier cells from diseased cells. In light of these considerations, we review the pathophysiology of LHON as it relates to old, new and future models. We further discuss treatments for LHON and unanswered questions that might be explored using these new model systems.
Leber 遗传性视神经病变（LHON）是一种主要影响视网膜神经节细胞（RGC）的线粒体疾病。由于历史上缺乏有效的疾病模型，LHON 的发病机制仍不清楚。最近有一些有前途的模型开始出现；然而，效果较差的模型仍然很受欢迎。许多此类模型使用非神经元细胞来代表 LHON，或者假设突变的 mtDNA 本身足以模拟疾病。这是有问题的，因为特定于上下文的因素在 LHON 的发病机制中起着重要作用，因为 mtDNA 突变本身是必要的，但不足以导致 LHON。有效的 LHON 模型应该能够证明区分健康载体细胞与患病细胞的过程。有鉴于此，我们回顾了 LHON 的病理生理学，以及与旧模型、新模型和未来模型的关系。我们进一步讨论了 LHON 的治疗方法以及使用这些新模型系统可能探索的未解决问题。
