Duarte Joao N
Neuroinflammation Unit, Biotech Research & Innovation Center, University of Copenhagen, Copenhagen, Denmark.
Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark.
J Ophthalmol. 2021 Apr 15;2021:4581909. doi: 10.1155/2021/4581909. eCollection 2021.
The exact mechanism of retinal ganglion cell loss in the pathogenesis of glaucoma is yet to be understood. Mitochondrial damage-associated molecular patterns (DAMPs) resulting from mitochondrial dysfunction have been linked to Leber's hereditary optic neuropathy and autosomal dominant optic atrophy, as well as to brain neurodegenerative diseases. Recent evidence shows that, in conditions where mitochondria are damaged, a sustained inflammatory response and downstream pathological inflammation may ensue. Mitochondrial damage has been linked to the accumulation of age-related mitochondrial DNA mutations and mitochondrial dysfunction, possibly through aberrant reactive oxygen species production and defective mitophagy. The present review focuses on how mitochondrial dysfunction may overwhelm the ability of neurons and glial cells to adequately maintain homeostasis and how mitochondria-derived DAMPs trigger the immune system and induce neurodegeneration.
青光眼发病机制中视网膜神经节细胞丢失的确切机制尚待明确。线粒体功能障碍产生的线粒体损伤相关分子模式（DAMPs）已与Leber遗传性视神经病变、常染色体显性视神经萎缩以及脑部神经退行性疾病相关联。最近的证据表明，在存在线粒体损伤的情况下，可能会随之出现持续的炎症反应以及下游病理性炎症。线粒体损伤可能与年龄相关的线粒体DNA突变积累和线粒体功能障碍有关，这可能是通过异常的活性氧产生和有缺陷的线粒体自噬实现的。本综述聚焦于线粒体功能障碍如何可能使神经元和神经胶质细胞充分维持内环境稳定的能力不堪重负，以及线粒体衍生的DAMPs如何触发免疫系统并诱导神经退行性变。
