Authors
Haitao Liu, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Sayan Ghosh, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Tanuja Vaidya, GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
Sridhar Bammidi, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Chao Huang, Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
Peng Shang, Doheny Eye Institute, Los Angeles, California, USA.
Archana Padmanabhan Nair, GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
Olivia Chowdhury, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Nadezda A. Stepicheva, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Anastasia Strizhakova, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Stacey Hose, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Nikolaos Mitrousis, Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
Santosh Gopikrishna Gadde, GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
Thirumalesh Mb, GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
Pamela Strassburger, Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
Gabriella Widmer, Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
Eleonora M. Lad, Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA.
Patrice E. Fort, Kellogg Eye Center, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
José-Alain Sahel, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
J Samuel Zigler, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Swaminathan Sethu, GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
Peter D. Westenskow, Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
A D. Proia, Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
Akrit Sodhi, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Arkasubhra Ghosh, GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
Derrick Feenstra, Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
Debasish Sinha, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Date of Publication
6-22-2023
Publication Title
JCI insight
Abstract
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.
DOI
10.1172/jci.insight.168945
Recommended Citation
Liu, Haitao; Ghosh, Sayan; Vaidya, Tanuja; Bammidi, Sridhar; Huang, Chao; Shang, Peng; Nair, Archana Padmanabhan; Chowdhury, Olivia; Stepicheva, Nadezda A.; Strizhakova, Anastasia; Hose, Stacey; Mitrousis, Nikolaos; Gadde, Santosh Gopikrishna; Mb, Thirumalesh; Strassburger, Pamela; Widmer, Gabriella; Lad, Eleonora M.; Fort, Patrice E.; Sahel, José-Alain; Zigler, J Samuel; Sethu, Swaminathan; Westenskow, Peter D.; Proia, A D.; Sodhi, Akrit; Ghosh, Arkasubhra; Feenstra, Derrick; and Sinha, Debasish, "Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy" (2023). Osteopathic Medicine, Jerry M. Wallace School of. 2410.
https://cufind.campbell.edu/medicine_school/2410
