Diabetes-mediated IL-17A enhances retinal inflammation, oxidative stress, and vascular permeability

Sigrun Sigurdardottir; Thomas E Zapadka; Sarah I Lindstrom; Haitao Liu; Brooklyn E Taylor; Chieh A Lee; Timothy S Kern; Patricia R Taylor

doi:10.1016/j.cellimm.2019.04.009

Diabetes-mediated IL-17A enhances retinal inflammation, oxidative stress, and vascular permeability

Cell Immunol. 2019 Jul:341:103921. doi: 10.1016/j.cellimm.2019.04.009. Epub 2019 May 2.

Authors

Sigrun Sigurdardottir¹, Thomas E Zapadka¹, Sarah I Lindstrom¹, Haitao Liu², Brooklyn E Taylor¹, Chieh A Lee², Timothy S Kern³, Patricia R Taylor⁴

Affiliations

¹ Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH, United States.
² Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, OH, United States.
³ Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, OH, United States; Louis Stokes VA Medical Center, Cleveland, OH, United States.
⁴ Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH, United States; Louis Stokes VA Medical Center, Cleveland, OH, United States. Electronic address: patricia.r.taylor@case.edu.

Abstract

Diabetic retinopathy is a prevailing diabetes complication, and one of the leading causes of blindness worldwide. IL-17A is a cytokine involved in the onset of diabetic complications. In the current study, we examined the role of IL-17A in the development of retinal inflammation and long-term vascular pathology in diabetic mice. We found IL-17A expressing T cells and neutrophils in the retinal vasculature. Further, the IL-17A receptor was expressed on Muller glia, retinal endothelial cells, and photoreceptors. Finally, diabetes-mediated retinal inflammation, oxidative stress, and vascular leakage were all significantly lower in IL-17A^-/- mice. These are all clinically meaningful abnormalities that characterize the onset of diabetic retinopathy.

Keywords: Diabetic retinopathy; IL-17A; Retinal pathology.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Capillary Permeability / genetics*
Capillary Permeability / immunology
Diabetes Mellitus, Experimental / genetics*
Diabetes Mellitus, Experimental / immunology
Diabetes Mellitus, Experimental / pathology
Diabetic Retinopathy / genetics*
Diabetic Retinopathy / immunology
Diabetic Retinopathy / pathology
Endothelial Cells / immunology*
Endothelial Cells / pathology
Ependymoglial Cells / immunology*
Ependymoglial Cells / pathology
Gene Expression Regulation
Inflammation
Interleukin-17 / deficiency
Interleukin-17 / genetics*
Interleukin-17 / immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils / immunology
Neutrophils / pathology
Oxidative Stress
Receptors, Interleukin-17 / genetics
Receptors, Interleukin-17 / immunology
Retinal Cone Photoreceptor Cells / immunology
Retinal Cone Photoreceptor Cells / pathology
Signal Transduction
Streptozocin
T-Lymphocytes / immunology
T-Lymphocytes / pathology

Substances

Il17a protein, mouse
Interleukin-17
Receptors, Interleukin-17
Streptozocin

Abstract

Publication types

MeSH terms

Substances

Grants and funding