Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults and remains an important public health issue worldwide. Here we demonstrate that the expression of stimulator of interferon genes (STING) is increased in patients with DR and animal models of diabetic eye disease. STING has been previously shown to regulate cell senescence and inflammation, key contributors to the development and progression of DR. To investigate the mechanism whereby STING contributes to the pathogenesis of DR, diabetes was induced in STING -KO mice and STING GT (loss-of-function mutation) mice, and molecular alterations and pathological changes in the retina were characterized. We report that retinal endothelial cell senescence, inflammation, and capillary degeneration were all inhibited in STING -KO diabetic mice; these observations were independently corroborated in STING GT mice. These protective effects resulted from the reduction in TBK1, IRF3, and NF-κB phosphorylation in the absence of STING. Collectively, our results suggest that targeting STING may be an effective therapy for the early prevention and treatment of DR.

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Background: Coronavirus disease (COVID-19) vaccines can cause adverse ocular effects, including vascular insults, acute macular neuroretinopathy, paracentral acute middle maculopathy (PAMM), ophthalmic vein thrombosis, Graves’ disease, arteritic anterior ischemic optic neuropathy (A-AION), and nonarteritic AION. Here, we report a case of unilateral PAMM progressing to central retinal artery occlusion (CRAO) after COVID-19 vaccination, identified using multimodal imaging. Case Presentation: A 24-year-old healthy man presented with unilateral progressive blurring of vision in the right eye. He had a recent history of fever without rashes 2 weeks after coronavirus disease vaccination. He was diagnosed with PAMM in the right eye at a local hospital and treated with a tapering dose of oral steroids. At presentation, he showed progressive blurring of vision in the right eye and the best-corrected distance visual acuity (BCDVA) was 20/60. The anterior segment was normal. Fundus examination revealed a pale optic disc with arteriolar attenuation and barrage laser scarring at the inferotemporal periphery. CRAO was diagnosed based on the right eye findings. The patient underwent multimodal imaging, including wide-field fundus photography using Optos® (Optos Carfornia®, Optos Inc., Dunfermline, United Kingdom), multicolor imaging with Spectralis™ (Heidelberg Retinal Angiograph; Heidelberg Engineering, Inc., Dossenheim, Germany), fundus fluorescence angiography (Heidelberg Retinal Angiograph; Heidelberg Engineering, Inc., Dossenheim, Germany), and optical coherence tomography angiography (ANGIOVUE, OPTOVUE, Inc., Fremont, CA, USA) using the split-spectrum amplitude-decorrelation angiography algorithm. The condition progressed from PAMM to CRAO during the oral steroid treatment course. At the 2-month follow-up, the right eye BCDVA had improved to 20/50, with fundus findings remaining the same as at the previous visit. Conclusions: This was the first report of a young patient with PAMM presenting with focal vascular occlusion that evolved to global occlusion in the form of CRAO in the absence of systemic vascular risk factors and with a normal coagulation profile. This case suggests that arterial occlusion may exert a temporary effect secondary to COVISHIELD™ vaccination. Randomized controlled trials and case – control studies on the role of vaccination in precipitating thromboembolic events in healthy individuals would provide insight into the causation.