Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
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
_version_ 1783256430332084224
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
work_keys_str_mv AT hammersandras themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT belieleni themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT kadynermin themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT wangqi themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT woodkiana themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT lydictodda themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT malekgoldis themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT sabandanielr themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT wangxiaoxinx themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT hazrasugata themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT levimoshe themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT busikjuliav themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT grantmariab themechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT hammersandras mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT belieleni mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT kadynermin mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT wangqi mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT woodkiana mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT lydictodda mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT malekgoldis mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT sabandanielr mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT wangxiaoxinx mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT hazrasugata mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT levimoshe mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT busikjuliav mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor
AT grantmariab mechanismofdiabeticretinopathypathogenesisunifyingkeylipidregulatorssirtuin1andliverxreceptor