LAUSR

Significance Ischemic retinopathy is a leading cause of blindness and has unmet medical needs for novel therapeutic strategies. In this work, we found that the cGAS-STING pathway was activated in the retina with ischemia-induced retinopathy, predominantly in myeloid cells. Disruption of cGAS-STING signaling alleviated retinal neovascularization and inflammation in the OIR model. Toward the mechanism for cGAS-STING activation in the OIR retina, we found that PPARα plays a significant role in suppressing the expression of cGAS and STING in ischemic retinopathy. These observations have revealed an interaction between PPARα and cGAS-STING signaling and have suggested that dysregulation of the cGAS-STING pathway is a pathogenic mechanism for myeloid cell overactivation and retinal neovascularization in ischemic retinopathy.