线粒体自噬与青光眼发病机制的关系

Relationship between mitochondrial autophagy and pathogenesis of glaucoma

线粒体自噬对维持线粒体网络正常功能起着重要作用,线粒体自噬通过清除受损的线粒体实现线粒体的更新.视网膜神经节细胞(retinal ganglion cells,RGCs)具有复杂的树突和极长的轴突.有非常高的能量需求.使其对线粒体功能障碍非常敏感,线粒体自噬受损与青光眼的发生发展密切相关OPTN基因和TBK1基因的突变分别与原发性开角型青光眼和正常眼压性青光眼相关,可能是由于基因突变引起线粒体自噬失调导致RGCs凋亡过表达线粒体自噬相关基因Parkin对RGCs具有保护作用。深入了解RGCs的线粒体功能障碍过程和线粒体自噬对其影响具有重要意义,可能为青光眼的预防、治疗提供新的方向。

Mitophagy plays a key role in the maintenance of a healthy and functional mitochondrial network in the cell by eliminating damaged mitochondria resulting in mitochondrial turnover. With complex dendritic arbors and long axons retinal ganglion cells ( RGCs) are highly energy demanding, it is not surprising that RGCs are particularly vulnerable to mitochondrial dysfunction. Mitophagy defect plays a pivotal role in the pathogenesis and development of glaucoma. Of interest, mutations in OPTN gene and TBK1 gene may lead to mitophagy dysfunction, and is associated with primary open angle glaucoma and normal-tension glaucoma ,respectively, as the result of RGCs apoptosis. Overexpression of parkin , a gene product of related to mitophagy, protects RGCs in animals with experimental glaucoma. Understanding of mitochondrial dysfunction and the role played by mitophagy in this process are of important scientific and clinical value, as it might provide novel approaches to the prevention and treatment of glaucoma.