| First Author | Lindstrom SI | Year | 2019 |
| Journal | J Diabetes Complications | Volume | 33 |
| Issue | 9 | Pages | 668-674 |
| PubMed ID | 31239234 | Mgi Jnum | J:298428 |
| Mgi Id | MGI:6480105 | Doi | 10.1016/j.jdiacomp.2019.05.016 |
| Citation | Lindstrom SI, et al. (2019) Diabetes induces IL-17A-Act1-FADD-dependent retinal endothelial cell death and capillary degeneration. J Diabetes Complications 33(9):668-674 |
| abstractText | PURPOSE: Diabetes leads to progressive complications such as diabetic retinopathy, which is the leading cause of blindness within the working-age population worldwide. Interleukin (IL)-17A is a cytokine that promotes and progresses diabetes. The objective of this study was to determine the role of IL-17A in retinal capillary degeneration, and to identify the mechanism that induces retinal endothelial cell death. These are clinically meaningful abnormalities that characterize early-stage non-proliferative diabetic retinopathy. METHODS: Retinal capillary degeneration was examined in vivo using the streptozotocin (STZ) diabetes murine model. Diabetic-hyperglycemia was sustained for an 8-month period in wild type (C57BL/6) and IL-17A(-/-) mice to elucidate the role of IL-17A in retinal capillary degeneration. Further, ex vivo studies were performed in retinal endothelial cells to identify the IL-17A-dependent mechanism that induces cell death. RESULTS: It was determined that diabetes-induced retinal capillary degeneration was significantly lower in IL-17A(-/-) mice. Further, retinal endothelial cell death occurred through an IL-17A/IL-17RAct1/FADD signaling cascade, which caused caspase-mediated apoptosis. CONCLUSION: These are the first findings that establish a pathologic role for IL-17A in retinal capillary degeneration. Further, a novel IL-17A-dependent apoptotic mechanism was discovered, which identifies potential therapeutic targets for the early onset of diabetic retinopathy. |
