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Article

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

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iNOVA4HEALTH, CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal
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ProRegeM PhD Programme—NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal
3
NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal
*
Author to whom correspondence should be addressed.
Academic Editors: Ana Raquel Santiago and Raquel Boia
Int. J. Mol. Sci. 2021, 22(21), 11402; https://doi.org/10.3390/ijms222111402
Received: 16 September 2021 / Revised: 10 October 2021 / Accepted: 12 October 2021 / Published: 22 October 2021
(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-O-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-O-sulfate treatment in RPE cells under high glucose and hypoxia. To test its effect on a diabetic mouse model, Ins2Akita 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-O-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-O-sulfate metabolite as a preventive approach towards DR progression, targeting molecules involved in both inflammation and neovascularization. View Full-Text
Keywords: diabetic retinopathy; inflammation; neovascularization; retinal pigment epithelium; hyperglycemia diabetic retinopathy; inflammation; neovascularization; retinal pigment epithelium; hyperglycemia
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MDPI and ACS Style

Santos, D.F.; Pais, M.; Santos, C.N.; Silva, G.A. Polyphenol Metabolite Pyrogallol-O-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina. Int. J. Mol. Sci. 2021, 22, 11402. https://doi.org/10.3390/ijms222111402

AMA Style

Santos DF, Pais M, Santos CN, Silva GA. Polyphenol Metabolite Pyrogallol-O-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina. International Journal of Molecular Sciences. 2021; 22(21):11402. https://doi.org/10.3390/ijms222111402

Chicago/Turabian Style

Santos, Daniela F., Mariana Pais, Cláudia N. Santos, and Gabriela A. Silva. 2021. "Polyphenol Metabolite Pyrogallol-O-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina" International Journal of Molecular Sciences 22, no. 21: 11402. https://doi.org/10.3390/ijms222111402

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