Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy.

Autor:	Liu H; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Ghosh S; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Vaidya T; GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India., Bammidi S; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Huang C; Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland., Shang P; Doheny Eye Institute, Los Angeles, California, USA., Nair AP; GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India., Chowdhury O; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Stepicheva NA; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Strizhakova A; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Hose S; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Mitrousis N; Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland., Gadde SG; GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India., Mb T; GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India., Strassburger P; Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland., Widmer G; Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland., Lad EM; Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA., Fort PE; Kellogg Eye Center, University of Michigan School of Medicine, Ann Arbor, Michigan, USA., Sahel JA; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Institut De La Vision, INSERM, CNRS, Sorbonne Université, Paris, France., Zigler JS Jr; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Sethu S; GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India., Westenskow PD; Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland., Proia AD; Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.; Department of Pathology, Campbell University Jerry M. Wallace School of Osteopathic Medicine, Lillington, North Carolina, USA., Sodhi A; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Ghosh A; GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India., Feenstra D; Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland., Sinha D; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2023 Jun 22; Vol. 8 (12). Date of Electronic Publication: 2023 Jun 22.
DOI:	10.1172/jci.insight.168945
Abstrakt:	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 STINGGT (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 STINGGT 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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu