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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...

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Autores principales: Robinson, Rebekah, Srinivasan, Mukund, Shanmugam, Arul, Ward, Alexander, Ganapathy, Veena, Bloom, Justin, Sharma, Ashok, Sharma, Shruti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231846/
https://www.ncbi.nlm.nih.gov/pubmed/32422539
http://dx.doi.org/10.1016/j.redox.2020.101574
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author Robinson, Rebekah
Srinivasan, Mukund
Shanmugam, Arul
Ward, Alexander
Ganapathy, Veena
Bloom, Justin
Sharma, Ashok
Sharma, Shruti
author_facet Robinson, Rebekah
Srinivasan, Mukund
Shanmugam, Arul
Ward, Alexander
Ganapathy, Veena
Bloom, Justin
Sharma, Ashok
Sharma, Shruti
author_sort Robinson, Rebekah
collection PubMed
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.
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spelling pubmed-72318462020-05-20 Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy Robinson, Rebekah Srinivasan, Mukund Shanmugam, Arul Ward, Alexander Ganapathy, Veena Bloom, Justin Sharma, Ashok Sharma, Shruti Redox Biol Research Paper 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. Elsevier 2020-05-13 /pmc/articles/PMC7231846/ /pubmed/32422539 http://dx.doi.org/10.1016/j.redox.2020.101574 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Robinson, Rebekah
Srinivasan, Mukund
Shanmugam, Arul
Ward, Alexander
Ganapathy, Veena
Bloom, Justin
Sharma, Ashok
Sharma, Shruti
Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy
title 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_short 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
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231846/
https://www.ncbi.nlm.nih.gov/pubmed/32422539
http://dx.doi.org/10.1016/j.redox.2020.101574
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