Fig. 9.

Pathogenic role of cGAS-STING signaling in ischemic retinopathy. Ischemic stress in the retinas transited the myeloid cells (including resident microglia and monocyte/macrophage derived from the bone marrow) from resting form to activated form. Downregulation of PPARα in the ischemic retina contributes to the mitochondrial stress, resulting in the release of mitochondrial DNA (mtDNA) into cytosol. Cytosolic mtDNA activated DNA sensor cGAS, which synthesized the second messenger 2′3′-cGAMP to activated downstream adaptor protein STING. Activation of cGAS-STING signaling in myeloid cells promoted the secretion of pro-inflammatory and pro-angiogenic cytokines, contributing to the inflammation and angiogenesis in ischemic retinas. The schematic figure was generated in BioRender.com.