Abu-Amero Khaled K
Department of Ophthalmology, Ophthalmic Genetics Laboratory, College of Medicine, King Saud University, P. O. Box 245, Riyadh 11411, Saudi Arabia.
Middle East Afr J Ophthalmol. 2011 Jan;18(1):17-23. doi: 10.4103/0974-9233.75880.
Our current understanding of Leber's hereditary optic neuropathy (LHON)-mitochondrial connection falls short of comprehensive. Twenty years of intensive investigation have yielded a wealth of information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and other structures, and the phenotypic variability of classic LHON. However, we still cannot completely explain how primary LHON mutations injure the optic nerve or why the optic nerve is particularly at risk. We cannot explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adult life without warning, or the synchronicity of visual loss. Moreover, primary LHON mutations clearly are not present in every family with the LHON phenotype (including multigenerational maternal inheritance), and they are present in only a minority of individuals who have the LHON optic neuropathy phenotype without a family history. All lines of evidence point to abnormalities of the mitochondria as the direct or indirect cause of LHON. Therefore, the mitochondria-LHON connection needs to be revisited and examined closely. This review will attempt to do that and provide an update on various aspects of LHON.
我们目前对莱伯遗传性视神经病变（LHON）与线粒体之间联系的理解并不全面。二十年的深入研究已经产生了大量关于线粒体、线粒体基因组、视神经及其他结构的代谢以及经典LHON表型变异性的信息。然而，我们仍然无法完全解释原发性LHON突变如何损伤视神经，或者为什么视神经特别容易受到影响。我们无法解释LHON的不完全外显率或男性优势、在年轻成年期无预警的典型发病，或者视力丧失的同步性。此外，原发性LHON突变显然并非在每个具有LHON表型的家族中都存在（包括多代母系遗传），并且仅在少数无家族病史但具有LHON视神经病变表型的个体中出现。所有证据都表明线粒体异常是LHON的直接或间接原因。因此，线粒体与LHON之间的联系需要重新审视并仔细研究。本综述将尝试做到这一点，并提供LHON各个方面的最新情况。
