cGAS-STING pathway-mediated inflammatory response and its role in corneal fibrosis mechanisms.

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway is a key innate immune mechanism that is responsible for sensing cytosolic DNA, mediating antiviral responses and triggering proinflammatory signaling. This pathway plays a vital role in clearing DNA viral infections, such as herpes simplex virus (HSV), and has also been increasingly recognized for its contribution to chronic inflammation and tissue fibrosis when aberrantly activated, thus serving as a crucial bridge between immune surveillance and pathological fibrogenesis. Corneal fibrosis, which often results from infection, immune dysregulation, or trauma, is primarily driven by an imbalance in inflammatory regulation and disordered wound healing. The activation of the cGAS-STING pathway facilitates the release of profibrotic cytokines and remodeling of the corneal stroma, thereby promoting the transdifferentiation of fibroblasts into myofibroblasts and the abnormal accumulation of the extracellular matrix, which ultimately leads to scarring and corneal opacity. This review provides a comprehensive overview of the immunoregulatory role of the cGAS-STING pathway in corneal and ocular diseases, with a focus on its involvement in postviral fibrosis. Furthermore, this study highlights the therapeutic potential of the targeting of this pathway via anti-inflammatory and antifibrotic strategies, thus offering new insights and molecular targets for clinical intervention.