Milea Dan, Amati-Bonneau Patrizia, Reynier Pascal, Bonneau Dominique
Department of Ophthalmology, Angers University Hospital, Angers, France.
Curr Opin Neurol. 2010 Feb;23(1):24-8. doi: 10.1097/WCO.0b013e3283347b27.
The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions.
Autosomal dominant optic atrophy, the most common hereditary optic neuropathy, appears to have a more variable clinical presentation than previously thought. Acute visual loss, reversible visual loss, or visual loss associated with extraocular symptoms (deafness, extraocular ophthalmoplegia, multiple sclerosis-like disease) are infrequent, though possible presentations. In Leber's hereditary optic neuropathy, recent findings suggest that the large variability of the clinical expression could be modulated by several factors: genetic (downregulation of the OPA1 gene), environmental (smoking), and anatomic (predisposition of the optic nerve head to axonal loss). Globally, hereditary optic neuropathies may represent an underestimated cause of unexplained and sporadic optic atrophy.Recent advances, such as the discovery of a new gene involved in autosomal recessive optic neuropathy, reinforce the central role played by mitochondrial dysfunctions in the pathogenesis of optic neuropathies.
Hereditary optic neuropathies may have a heterogenous presentation and serve as a paradigm for neurodegenerative diseases affecting mitochondrial structure, plasticity, and function.
本综述聚焦于主要由线粒体功能障碍导致视网膜神经节细胞变性所引起的遗传性视神经病变的最新研究进展。
常染色体显性遗传性视神经萎缩是最常见的遗传性视神经病变，其临床表现似乎比之前认为的更具多样性。急性视力丧失、可逆性视力丧失或伴有眼外症状（耳聋、眼外肌麻痹、多发性硬化样疾病）的视力丧失虽有可能出现，但并不常见。在Leber遗传性视神经病变中，最新研究结果表明，临床表型的巨大差异可能受多种因素调节：基因（OPA1基因下调）、环境（吸烟）以及解剖学因素（视神经乳头易发生轴突丢失）。总体而言，遗传性视神经病变可能是不明原因和散发性视神经萎缩被低估的一个原因。最近的进展，如发现一个与常染色体隐性遗传性视神经病变相关的新基因，进一步强化了线粒体功能障碍在视神经病变发病机制中所起的核心作用。
遗传性视神经病变可能具有异质性表现，并可作为影响线粒体结构、可塑性和功能的神经退行性疾病的范例。
