SCIENCE@home

Diabetes induces IL-17A-Act1-FADD-dependent retinal endothelial cell death and capillary degeneration.

Sarah I. Lindstrom,S. Sigurdardottir,Thomas E. Zapadka,Jie-long Tang,Haitao Liu,Brooklyn E. Taylor,Dawn G. Smith,CHIEH-ALLEN Lee,John DeAngelis,T. Kern,Patricia R. Taylor

Published 2019 in Journal of diabetes and its complications

ABSTRACT

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-17R ➔ Act1/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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-28 of 28 references · Page 1 of 1

CITED BY

Showing 1-35 of 35 citing papers · Page 1 of 1