Targeting the cGAS-STING pathway in ophthalmology: from innate immunity to therapeutic innovation

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a key mediator of the innate immune response to cytosolic DNA, with growing implications beyond traditional host defense mechanisms. Recent research has linked the abnormal activation of this pathway to a wide range of ocular diseases, such as age-related macular degeneration, diabetic retinopathy, corneal injuries, glaucoma, and ocular tumors. This review examines the multifaceted roles of cGAS-STING signaling in ocular inflammation, tissue degeneration, fibrosis, angiogenesis, and immune surveillance. We emphasize the mechanistic basis through which the cGAS-STING pathway orchestrates various pathological processes across different ocular compartments, from the ocular surface to the retina. Additionally, we discuss its interactions with autophagy, cellular senescence, and cell death, exploring its potential as a therapeutic target in inflammatory and neoplastic eye conditions. Finally, we identify key unresolved questions and outline future research directions aimed at exploiting cGAS-STING modulation for precision therapies in vision-threatening diseases.