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.
Haitao Liu, Sayan Ghosh, Tanuja Vaidya, Sridhar Bammidi, Chao Huang, Peng Shang, Archana Padmanabhan Nair, Olivia Chowdhury, Nadezda A. Stepicheva, Anastasia Strizhakova, Stacey Hose, Nikolaos Mitrousis, Santosh Gopikrishna Gadde, Thirumalesh MB, Pamela Strassburger, Gabriella Widmer, Eleonora M. Lad, Patrice E. Fort, José-Alain Sahel, J. Samuel Zigler Jr., Swaminathan Sethu, Peter D. Westenskow, Alan D. Proia, Akrit Sodhi, Arkasubhra Ghosh, Derrick Feenstra, Debasish Sinha
Usage data is cumulative from June 2023 through June 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 3,623 | 1,816 |
593 | 530 | |
Figure | 937 | 48 |
Supplemental data | 158 | 33 |
Citation downloads | 53 | 0 |
Totals | 5,364 | 2,427 |
Total Views | 7,791 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.