细胞衰老在青光眼中的作用研究进展

Research progress of cellular senescence in glaucoma

细胞衰老是细胞在缺血、缺氧、氧化应激、DNA损伤、活性氧沉积等刺激下被激活的一种应答程序。衰老细胞的特征包括:衰老相关β-半乳糖苷酶(SA-β-gal)活性升高、P16INK4a高表达、衰老相关易染色质(SAHF)聚集、衰老相关分泌表型(SASP)产生、端粒缩短等。介导细胞衰老的经典信号通路包括P16INK4a/Rb途径和P19 ARF/P53/P21 Cip1途径,这2条通路既相互作用,又相互独立。近年来,青光眼被认为是与细胞衰老密切相关的致盲眼病。细胞衰老在青光眼中的研究主要集中在小梁网和Schlemm管内皮细胞衰老引起房水流出通路阻力增加,以及细胞衰老在青光眼视网膜神经节细胞损伤中的作用机制及干预研究。细胞衰老作为细胞死亡前的不可逆阶段,深入研究其在青光眼发生和发展中的作用机制,并特异性阻断细胞衰老信号传递,有助于为降低房水流出阻力和青光眼视神经保护治疗提供新的切入点。本文就细胞衰老的特征、诱因、分子信号通路以及其在青光眼中的研究进展进行综述。

Cellular senescence is a response process in which cells are activated by ischemia,hypoxia,oxidative stress,DNA damage,reactive oxygen species deposition and other stimulations.Senescent cells markers include such as senescence-associatedβ-galactosidase(SA-β-gal)activation,P16INK4a upregualtion,senescence-associated heterochromatic foci(SAHF)accumulation,senescence-associated secretory phenotype(SASP)generation,telomere shortening and so on.P16INK4a/Rb and P19 ARF/P53/P21 Cip1 pathways are two classic cell senescence signaling pathways,which are interconnected and independent on each other.In recent years,glaucoma is considered as a blinding eye disease associated with cell senescence.Research on cell senescence in glaucoma mainly focuses on trabecular meshwork and Schlemm cannel endothelial cells senescence leading to increased resistance of aqueous humor outflow pathway,and the mechanism of retinal ganglion cells senescence and treatment in glaucoma.As an irreversible stage before cell death,deeper study on the mechanism of retinal ganglion cells senescence,and specific blocking of cell senescence will provide a new target for reducing the aqueous humor outflow resistance and protecting the optic nerve in glaucoma.This article reviewed characteristics,inducements,molecular signaling pathways of cellular senescence in glaucoma.