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The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor
Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Several clinical trials have highlighted the vital...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552206/ https://www.ncbi.nlm.nih.gov/pubmed/28774737 http://dx.doi.org/10.1016/j.ebiom.2017.07.008 |
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author | Hammer, Sandra S. Beli, Eleni Kady, Nermin Wang, Qi Wood, Kiana Lydic, Todd A. Malek, Goldis Saban, Daniel R. Wang, Xiaoxin X. Hazra, Sugata Levi, Moshe Busik, Julia V. Grant, Maria B. |
author_facet | Hammer, Sandra S. Beli, Eleni Kady, Nermin Wang, Qi Wood, Kiana Lydic, Todd A. Malek, Goldis Saban, Daniel R. Wang, Xiaoxin X. Hazra, Sugata Levi, Moshe Busik, Julia V. Grant, Maria B. |
author_sort | Hammer, Sandra S. |
collection | PubMed |
description | Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Several clinical trials have highlighted the vital role dyslipidemia plays in the progression of DR. Additionally, it has recently been shown that activation of Liver X receptor (LXRα/LXRβ) prevents DR in diabetic animal models. LXRs are nuclear receptors that play key roles in regulating cholesterol metabolism, fatty acid metabolism and inflammation. In this manuscript, we show insight into DR pathogenesis by demonstrating an innovative signaling axis that unifies key metabolic regulators, Sirtuin 1 and LXR, in modulating retinal cholesterol metabolism and inflammation in the diabetic retina. Expression of both regulators, Sirtuin 1 and LXR, are significantly decreased in diabetic human retinal samples and in a type 2 diabetic animal model. Additionally, activation of LXR restores reverse cholesterol transport, prevents inflammation, reduces pro-inflammatory macrophages activity and prevents the formation of diabetes-induced acellular capillaries. Taken together, the work presented in this manuscript highlights the important role lipid dysregulation plays in DR progression and offers a novel potential therapeutic target for the treatment of DR. |
format | Online Article Text |
id | pubmed-5552206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-55522062017-08-22 The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor Hammer, Sandra S. Beli, Eleni Kady, Nermin Wang, Qi Wood, Kiana Lydic, Todd A. Malek, Goldis Saban, Daniel R. Wang, Xiaoxin X. Hazra, Sugata Levi, Moshe Busik, Julia V. Grant, Maria B. EBioMedicine Research Paper Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Several clinical trials have highlighted the vital role dyslipidemia plays in the progression of DR. Additionally, it has recently been shown that activation of Liver X receptor (LXRα/LXRβ) prevents DR in diabetic animal models. LXRs are nuclear receptors that play key roles in regulating cholesterol metabolism, fatty acid metabolism and inflammation. In this manuscript, we show insight into DR pathogenesis by demonstrating an innovative signaling axis that unifies key metabolic regulators, Sirtuin 1 and LXR, in modulating retinal cholesterol metabolism and inflammation in the diabetic retina. Expression of both regulators, Sirtuin 1 and LXR, are significantly decreased in diabetic human retinal samples and in a type 2 diabetic animal model. Additionally, activation of LXR restores reverse cholesterol transport, prevents inflammation, reduces pro-inflammatory macrophages activity and prevents the formation of diabetes-induced acellular capillaries. Taken together, the work presented in this manuscript highlights the important role lipid dysregulation plays in DR progression and offers a novel potential therapeutic target for the treatment of DR. Elsevier 2017-07-11 /pmc/articles/PMC5552206/ /pubmed/28774737 http://dx.doi.org/10.1016/j.ebiom.2017.07.008 Text en © 2017 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 Hammer, Sandra S. Beli, Eleni Kady, Nermin Wang, Qi Wood, Kiana Lydic, Todd A. Malek, Goldis Saban, Daniel R. Wang, Xiaoxin X. Hazra, Sugata Levi, Moshe Busik, Julia V. Grant, Maria B. The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor |
title | The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor |
title_full | The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor |
title_fullStr | The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor |
title_full_unstemmed | The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor |
title_short | The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor |
title_sort | mechanism of diabetic retinopathy pathogenesis unifying key lipid regulators, sirtuin 1 and liver x receptor |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552206/ https://www.ncbi.nlm.nih.gov/pubmed/28774737 http://dx.doi.org/10.1016/j.ebiom.2017.07.008 |
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