An Emerging Role of Alu RNA in Geographic Atrophy Pathogenesis: the Implication for Novel Therapeutic Strategies

作者：Mao, Xiying; Fang, Wangyi; Liu, Qinghuai^*

来源：Discovery Medicine, 2016, 22(123): 337-349.

• NLRP3 INFLAMMASOME ACTIVATION
• OXIDATIVE STRESS
• MACULAR DEGENERATION
• CELL-DEATH
• RETINAL DYSTROPHIES
• MITOCHONDRIAL-DNA
• GENE-REGULATION
• KAPPA-B
• APOPTOSIS
• CASPASE-8

It is generally accepted that geographic atrophy (GA), a currently untreatable advanced form of age-related macular degeneration (AMD), is a multifactorial disease resulting in gradual and permanent blindness. Various risk factors are demonstrated to be responsible for its pathogenesis, such as aging, light exposure, and smoking. Molecular components associated with those risk factors form a complex and interwoven network at the confluence of inflammation, highlighting the significance of inflammasome activation in GA progression. Recently, a new type of modification in AMD microenvironment has been discovered, other than extensively-studied complement dysregulation, lipofuscin deposit, and oxidative by-products, to activate inflammasome. The accumulation of Alu RNA, resulting from DICER1 deficiency, is shown capable of triggering the activation of NLRP3 inflammasome and causing caspase-8-activated apoptosis in an IL-18/MyD88-dependent manner, which provides a new source of evidence for the interplay between cell death and inflammasome. In this review, we lay the emphasis on the mechanism by which Alu RNA activates NLRP3 inflammasome and downstream apoptotic proteins, and on its clinical relevance to GA and potential therapeutic approaches. We also point out several possible crosstalks among inflammasome and different acts of cell death which remain to be further investigated in Alu RNA-induced RPE degeneration.

• 出版日期2016-12
• 单位南京医科大学