Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy
Purpose: Diabetic retinopathy (DR), a microvascular complication of diabetes, is the leading cause of visual disability and blindness in diabetic patients. Chronic hyperglycemia leads to increased oxidative stress and inflammation in the retina, resulting in microvascular damage. Our recent in vitro...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2020-07-01
|
Series: | Redox Biology |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231720300720 |
id |
doaj-c23f643302b24b8eb177792147344ab1 |
---|---|
record_format |
Article |
spelling |
doaj-c23f643302b24b8eb177792147344ab12020-11-25T03:16:17ZengElsevierRedox Biology2213-23172020-07-0134101574Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathyRebekah Robinson0Mukund Srinivasan1Arul Shanmugam2Alexander Ward3Veena Ganapathy4Justin Bloom5Ashok Sharma6Shruti Sharma7Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA; Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA, USA; Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, GA, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA; Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA, USA; Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA, USA; Corresponding author. Center for Biotechnology and Genomic Medicine, 1120 15th street, CA4139, Augusta University, Augusta, GA, 30912, USA.Purpose: Diabetic retinopathy (DR), a microvascular complication of diabetes, is the leading cause of visual disability and blindness in diabetic patients. Chronic hyperglycemia leads to increased oxidative stress and inflammation in the retina, resulting in microvascular damage. Our recent in vitro studies have demonstrated that inhibition of interleukin-6 (IL-6) trans-signaling significantly reduces oxidative stress in retinal endothelial cells. The purpose of this study was to further explore the relationship between IL-6 trans-signaling and oxidative stress using a streptozotocin (STZ) induced mouse model of early diabetic retinopathy. Methods: Diabetes was induced in eight week-old male C57BL/6J mice using STZ injections. sgp130Fc (mouse sgp130Fc protein) treatment was used for inhibition of IL-6 trans-signaling. Studies were conducted to evaluate the effects of IL-6 trans-signaling on oxidative balance at the systemic and retinal level. Results: Decreased antioxidant capacity and increased oxidative stress was observed in diabetic mice, which returned to near-normal levels with sgp130Fc treatment. Similarly, superoxide levels, lipid peroxidation, and markers of oxidative DNA damage were increased in the diabetic retina, and these effects were abrogated by sgp130Fc treatment. Inhibition of IL-6 trans-signaling also restored normal expression of catalase and endothelial nitric oxide synthase in mouse retinas. Conclusions: Inhibition of IL-6 trans-signaling significantly reduces diabetes-induced oxidative damage at the systemic level and in the retina. These findings provide further evidence for the role of IL-6 trans-signaling in diabetes-mediated oxidative stress.http://www.sciencedirect.com/science/article/pii/S2213231720300720Diabetic retinopathyOxidative stressIL-6 trans-signaling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rebekah Robinson Mukund Srinivasan Arul Shanmugam Alexander Ward Veena Ganapathy Justin Bloom Ashok Sharma Shruti Sharma |
spellingShingle |
Rebekah Robinson Mukund Srinivasan Arul Shanmugam Alexander Ward Veena Ganapathy Justin Bloom Ashok Sharma Shruti Sharma Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy Redox Biology Diabetic retinopathy Oxidative stress IL-6 trans-signaling |
author_facet |
Rebekah Robinson Mukund Srinivasan Arul Shanmugam Alexander Ward Veena Ganapathy Justin Bloom Ashok Sharma Shruti Sharma |
author_sort |
Rebekah Robinson |
title |
Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy |
title_short |
Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy |
title_full |
Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy |
title_fullStr |
Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy |
title_full_unstemmed |
Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy |
title_sort |
interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2020-07-01 |
description |
Purpose: Diabetic retinopathy (DR), a microvascular complication of diabetes, is the leading cause of visual disability and blindness in diabetic patients. Chronic hyperglycemia leads to increased oxidative stress and inflammation in the retina, resulting in microvascular damage. Our recent in vitro studies have demonstrated that inhibition of interleukin-6 (IL-6) trans-signaling significantly reduces oxidative stress in retinal endothelial cells. The purpose of this study was to further explore the relationship between IL-6 trans-signaling and oxidative stress using a streptozotocin (STZ) induced mouse model of early diabetic retinopathy. Methods: Diabetes was induced in eight week-old male C57BL/6J mice using STZ injections. sgp130Fc (mouse sgp130Fc protein) treatment was used for inhibition of IL-6 trans-signaling. Studies were conducted to evaluate the effects of IL-6 trans-signaling on oxidative balance at the systemic and retinal level. Results: Decreased antioxidant capacity and increased oxidative stress was observed in diabetic mice, which returned to near-normal levels with sgp130Fc treatment. Similarly, superoxide levels, lipid peroxidation, and markers of oxidative DNA damage were increased in the diabetic retina, and these effects were abrogated by sgp130Fc treatment. Inhibition of IL-6 trans-signaling also restored normal expression of catalase and endothelial nitric oxide synthase in mouse retinas. Conclusions: Inhibition of IL-6 trans-signaling significantly reduces diabetes-induced oxidative damage at the systemic level and in the retina. These findings provide further evidence for the role of IL-6 trans-signaling in diabetes-mediated oxidative stress. |
topic |
Diabetic retinopathy Oxidative stress IL-6 trans-signaling |
url |
http://www.sciencedirect.com/science/article/pii/S2213231720300720 |
work_keys_str_mv |
AT rebekahrobinson interleukin6transsignalinginhibitionpreventsoxidativestressinamousemodelofearlydiabeticretinopathy AT mukundsrinivasan interleukin6transsignalinginhibitionpreventsoxidativestressinamousemodelofearlydiabeticretinopathy AT arulshanmugam interleukin6transsignalinginhibitionpreventsoxidativestressinamousemodelofearlydiabeticretinopathy AT alexanderward interleukin6transsignalinginhibitionpreventsoxidativestressinamousemodelofearlydiabeticretinopathy AT veenaganapathy interleukin6transsignalinginhibitionpreventsoxidativestressinamousemodelofearlydiabeticretinopathy AT justinbloom interleukin6transsignalinginhibitionpreventsoxidativestressinamousemodelofearlydiabeticretinopathy AT ashoksharma interleukin6transsignalinginhibitionpreventsoxidativestressinamousemodelofearlydiabeticretinopathy AT shrutisharma interleukin6transsignalinginhibitionpreventsoxidativestressinamousemodelofearlydiabeticretinopathy |
_version_ |
1724637166619852800 |