Polyphenol Metabolite Pyrogallol-<i>O</i>-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina

(Poly)phenol-derived metabolites are small molecules resulting from (poly)phenol metabolization after ingestion that can be found in circulation. In the last decade, studies on the impact of (poly)phenol properties in health and cellular metabolism accumulated evidence that (poly)phenols are benefic...

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Autores principales:	Daniela F. Santos, Mariana Pais, Cláudia N. Santos, Gabriela A. Silva
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	diabetic retinopathy inflammation neovascularization retinal pigment epithelium hyperglycemia Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5ef8962fd9314a03b559b9c5efb19787
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spelling	oai:doaj.org-article:5ef8962fd9314a03b559b9c5efb197872021-11-11T16:52:40ZPolyphenol Metabolite Pyrogallol-<i>O</i>-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina10.3390/ijms2221114021422-00671661-6596https://doaj.org/article/5ef8962fd9314a03b559b9c5efb197872021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11402https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067(Poly)phenol-derived metabolites are small molecules resulting from (poly)phenol metabolization after ingestion that can be found in circulation. In the last decade, studies on the impact of (poly)phenol properties in health and cellular metabolism accumulated evidence that (poly)phenols are beneficial against human diseases. Diabetic retinopathy (DR) is characterized by inflammation and neovascularization and targeting these is of therapeutic interest. We aimed to study the effect of pyrogallol-<i>O</i>-sulfate (Pyr-s) metabolite in the expression of proteins involved in retinal glial activation, neovascularization, and glucose transport. The expression of PEDF, VEGF, and GLUT-1 were analyzed upon pyrogallol-<i>O</i>-sulfate treatment in RPE cells under high glucose and hypoxia. To test its effect on a diabetic mouse model, Ins2<sup>Akita</sup> mice were subjected to a single intraocular injection of the metabolite and the expression of PEDF, VEGF, GLUT-1, Iba1, or GFAP measured in the neural retina and/or retinal pigment epithelium (RPE), two weeks after treatment. We observed a significant decrease in the expression of pro-angiogenic VEGF in RPE cells. Moreover, pyrogallol-<i>O</i>-sulfate significantly decreased the expression of microglial marker Iba1 in the diabetic retina at different stages of disease progression. These results highlight the potential pyrogallol-<i>O</i>-sulfate metabolite as a preventive approach towards DR progression, targeting molecules involved in both inflammation and neovascularization.Daniela F. SantosMariana PaisCláudia N. SantosGabriela A. SilvaMDPI AGarticlediabetic retinopathyinflammationneovascularizationretinal pigment epitheliumhyperglycemiaBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11402, p 11402 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetic retinopathy inflammation neovascularization retinal pigment epithelium hyperglycemia Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	diabetic retinopathy inflammation neovascularization retinal pigment epithelium hyperglycemia Biology (General) QH301-705.5 Chemistry QD1-999 Daniela F. Santos Mariana Pais Cláudia N. Santos Gabriela A. Silva Polyphenol Metabolite Pyrogallol-<i>O</i>-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina
description	(Poly)phenol-derived metabolites are small molecules resulting from (poly)phenol metabolization after ingestion that can be found in circulation. In the last decade, studies on the impact of (poly)phenol properties in health and cellular metabolism accumulated evidence that (poly)phenols are beneficial against human diseases. Diabetic retinopathy (DR) is characterized by inflammation and neovascularization and targeting these is of therapeutic interest. We aimed to study the effect of pyrogallol-<i>O</i>-sulfate (Pyr-s) metabolite in the expression of proteins involved in retinal glial activation, neovascularization, and glucose transport. The expression of PEDF, VEGF, and GLUT-1 were analyzed upon pyrogallol-<i>O</i>-sulfate treatment in RPE cells under high glucose and hypoxia. To test its effect on a diabetic mouse model, Ins2<sup>Akita</sup> mice were subjected to a single intraocular injection of the metabolite and the expression of PEDF, VEGF, GLUT-1, Iba1, or GFAP measured in the neural retina and/or retinal pigment epithelium (RPE), two weeks after treatment. We observed a significant decrease in the expression of pro-angiogenic VEGF in RPE cells. Moreover, pyrogallol-<i>O</i>-sulfate significantly decreased the expression of microglial marker Iba1 in the diabetic retina at different stages of disease progression. These results highlight the potential pyrogallol-<i>O</i>-sulfate metabolite as a preventive approach towards DR progression, targeting molecules involved in both inflammation and neovascularization.
format	article
author	Daniela F. Santos Mariana Pais Cláudia N. Santos Gabriela A. Silva
author_facet	Daniela F. Santos Mariana Pais Cláudia N. Santos Gabriela A. Silva
author_sort	Daniela F. Santos
title	Polyphenol Metabolite Pyrogallol-<i>O</i>-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina
title_short	Polyphenol Metabolite Pyrogallol-<i>O</i>-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina
title_full	Polyphenol Metabolite Pyrogallol-<i>O</i>-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina
title_fullStr	Polyphenol Metabolite Pyrogallol-<i>O</i>-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina
title_full_unstemmed	Polyphenol Metabolite Pyrogallol-<i>O</i>-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina
title_sort	polyphenol metabolite pyrogallol-<i>o</i>-sulfate decreases microglial activation and vegf in retinal pigment epithelium cells and diabetic mouse retina
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5ef8962fd9314a03b559b9c5efb19787
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Polyphenol Metabolite Pyrogallol-<i>O</i>-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina

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