The cGAS/STING pathway: A sensor of senescence-associated DNA damage and trigger of inflammation in early age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly. Considering the relatively limited effect of therapy on early AMD, it is important to focus on the pathogenesis of AMD, especially early AMD. Ageing is one of the strongest risk factors for AMD, and analysis of the impact of ageing on AMD development is valuable. Among all the ageing hallmarks, increased DNA damage accumulation is regarded as the beginning of cellular senescence and is related to abnormal expression of inflammatory cytokines, which is called the senescence-associated secretory phenotype (SASP). The exact pathway for DNA damage that triggers senescence-associated hallmarks is poorly understood. Recently, mounting evidence has shown that the cGAS/ STING pathway is an important DNA sensor related to proinflammatory factor secretion and is associated with another hallmark of ageing, SASP. Thus, we hypothesized that the cGAS/ STING pathway is a vital signalling pathway for early AMD development and that inhibition of STING might be a potential therapeutic strategy for AMD cases.