Doheny Eye Centers, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Doheny Eye Institute, Los Angeles, CA, USA.
Curr Neurol Neurosci Rep. 2020 Apr 15;20(5):11. doi: 10.1007/s11910-020-01032-8.
Leber's hereditary optic neuropathy (LHON) is a genetic disease of the mitochondrial genome that mainly affects the retinal ganglion cells (RGC) of the inner retina resulting in central vision loss. New understandings in mitochondrial genetics are helping to elucidate the nuances of conversion and allow for new therapeutic options.
Appreciation of the mitochondrial fission-fusion balance has allowed for increased understanding of the cascade of events that leads to clinical conversion in LOHN. Mathematical and computational models have helped to interpret the role of ROS in conversion, both as oxidative agents and as signaling molecules for cell death. The conversion from the LHON carrier to the affected patient has been clinically characterized, but the pathophysiology is just beginning to be understood. External stressors alter the mitochondrial dynamics of RGCs, leading to ROS buildup, energy shortages, decreased biogenesis and increased mitophagy, and ultimately axon degeneration and ganglion cell death. New therapeutic alternatives targeting these newly understood pathophysiological changes in the mitochondria and directly addressing the genetic mutations involved in LHON are being developed.
Leber 遗传性视神经病变（LHON）是一种线粒体基因组的遗传性疾病，主要影响视网膜内层的神经节细胞（RGC），导致中心视力丧失。线粒体遗传学的新认识有助于阐明转化的细微差别，并为新的治疗选择提供依据。
对线粒体分裂-融合平衡的认识增加了对导致 LHON 临床转化的一系列事件的理解。数学和计算模型有助于解释 ROS 在转化中的作用，既是氧化剂，又是细胞死亡的信号分子。从 LHON 携带者到受影响的患者的转化已经在临床上得到了描述，但病理生理学才刚刚开始被理解。外部应激源改变了 RGC 的线粒体动力学，导致 ROS 积累、能量短缺、生物发生减少和自噬增加，最终导致轴突退化和神经节细胞死亡。新的治疗选择针对线粒体中这些新理解的病理生理变化，并直接针对 LHON 中涉及的遗传突变，正在被开发。
