cGAS-STING-driven inflammaging cascade in aging-related retinal diseases: From pathological mechanism to therapeutic potentials

Abstract

Aging-related retinal diseases lead to irreversible structural damages and vision loss. These conditions are characterized by cellular senescence, oxidative stress, neural degeneration, and neovascularization. Among these, chronic inflammation is a hallmark of aging, establishing a self-perpetuating vicious cycle that accelerates pathological process and physiological decline. cGAS-STING signaling pathway has been identified as a critical mediator of inflammation across multiple retinal disease contexts, functioning to regulate immune response by detecting the dsDNA resulted from tissue injury. Under pathological circumstances, it exhibits a state of persistent activation, which results in chronic inflammatory reactions in the microenvironment. The disrupted homeostasis is closely linked with the onset and progression of numerous aging-related retinal diseases. Given the strong association between cGAS-STING signaling and these conditions, this pathway may represent a promising therapeutic target for refractory retinopathies. Encouragingly, several inhibitors targeting this pathway have already been developed and yielded remarkable therapeutic outcomes. This review delineates the primary functioning factors and modulatory mechanisms of the cGAS-STING cascade. Furthermore, it discusses the specific role of cGAS-STING pathway in pathological process of age-related retinopathy and summarize the key inhibitors of the cGAS-STING pathway, highlighting their therapeutic potentials for age-related retinopathy. These findings will deepen the understanding of the crosstalk between cGAS-STING signaling and retinal aging, thus offering valuable insights for the future translation of laboratory findings into clinical interventions.