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Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models
Retinal vascular leakage, inflammation, and neovascularization (NV) are features of diabetic retinopathy (DR). Fenofibrate, a peroxisome proliferator–activated receptor α (PPARα) agonist, has shown robust protective effects against DR in type 2 diabetic patients, but its effects on DR in type 1 diab...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526044/ https://www.ncbi.nlm.nih.gov/pubmed/23043158 http://dx.doi.org/10.2337/db11-0413 |
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author | Chen, Ying Hu, Yang Lin, Mingkai Jenkins, Alicia J. Keech, Anthony C. Mott, Robert Lyons, Timothy J. Ma, Jian-xing |
author_facet | Chen, Ying Hu, Yang Lin, Mingkai Jenkins, Alicia J. Keech, Anthony C. Mott, Robert Lyons, Timothy J. Ma, Jian-xing |
author_sort | Chen, Ying |
collection | PubMed |
description | Retinal vascular leakage, inflammation, and neovascularization (NV) are features of diabetic retinopathy (DR). Fenofibrate, a peroxisome proliferator–activated receptor α (PPARα) agonist, has shown robust protective effects against DR in type 2 diabetic patients, but its effects on DR in type 1 diabetes have not been reported. This study evaluated the efficacy of fenofibrate on DR in type 1 diabetes models and determined if the effect is PPARα dependent. Oral administration of fenofibrate significantly ameliorated retinal vascular leakage and leukostasis in streptozotocin-induced diabetic rats and in Akita mice. Favorable effects on DR were also achieved by intravitreal injection of fenofibrate or another specific PPARα agonist. Fenofibrate also ameliorated retinal NV in the oxygen-induced retinopathy (OIR) model and inhibited tube formation and migration in cultured endothelial cells. Fenofibrate also attenuated overexpression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and vascular endothelial growth factor (VEGF) and blocked activation of hypoxia-inducible factor-1 and nuclear factor-κB in the retinas of OIR and diabetic models. Fenofibrate’s beneficial effects were blocked by a specific PPARα antagonist. Furthermore, Pparα knockout abolished the fenofibrate-induced downregulation of VEGF and reduction of retinal vascular leakage in DR models. These results demonstrate therapeutic effects of fenofibrate on DR in type 1 diabetes and support the existence of the drug target in ocular tissues and via a PPARα-dependent mechanism. |
format | Online Article Text |
id | pubmed-3526044 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-35260442014-01-01 Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models Chen, Ying Hu, Yang Lin, Mingkai Jenkins, Alicia J. Keech, Anthony C. Mott, Robert Lyons, Timothy J. Ma, Jian-xing Diabetes Complications Retinal vascular leakage, inflammation, and neovascularization (NV) are features of diabetic retinopathy (DR). Fenofibrate, a peroxisome proliferator–activated receptor α (PPARα) agonist, has shown robust protective effects against DR in type 2 diabetic patients, but its effects on DR in type 1 diabetes have not been reported. This study evaluated the efficacy of fenofibrate on DR in type 1 diabetes models and determined if the effect is PPARα dependent. Oral administration of fenofibrate significantly ameliorated retinal vascular leakage and leukostasis in streptozotocin-induced diabetic rats and in Akita mice. Favorable effects on DR were also achieved by intravitreal injection of fenofibrate or another specific PPARα agonist. Fenofibrate also ameliorated retinal NV in the oxygen-induced retinopathy (OIR) model and inhibited tube formation and migration in cultured endothelial cells. Fenofibrate also attenuated overexpression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and vascular endothelial growth factor (VEGF) and blocked activation of hypoxia-inducible factor-1 and nuclear factor-κB in the retinas of OIR and diabetic models. Fenofibrate’s beneficial effects were blocked by a specific PPARα antagonist. Furthermore, Pparα knockout abolished the fenofibrate-induced downregulation of VEGF and reduction of retinal vascular leakage in DR models. These results demonstrate therapeutic effects of fenofibrate on DR in type 1 diabetes and support the existence of the drug target in ocular tissues and via a PPARα-dependent mechanism. American Diabetes Association 2013-01 2012-12-13 /pmc/articles/PMC3526044/ /pubmed/23043158 http://dx.doi.org/10.2337/db11-0413 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Complications Chen, Ying Hu, Yang Lin, Mingkai Jenkins, Alicia J. Keech, Anthony C. Mott, Robert Lyons, Timothy J. Ma, Jian-xing Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models |
title | Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models |
title_full | Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models |
title_fullStr | Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models |
title_full_unstemmed | Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models |
title_short | Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models |
title_sort | therapeutic effects of pparα agonists on diabetic retinopathy in type 1 diabetes models |
topic | Complications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526044/ https://www.ncbi.nlm.nih.gov/pubmed/23043158 http://dx.doi.org/10.2337/db11-0413 |
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