Hyperglycemia-induced VEGF and ROS production in retinal cells is inhibited by the mTOR inhibitor, rapamycin

Abstract Determine the impact of the mTOR inhibitor, rapamycin, on the hyperglycemia-induced expression of vascular endothelial growth factor (VEGF) and the production of reactive oxygen species (ROS) in retinal cells. Rats made hyperglycemic for 8 weeks by streptozotocin, as well as control rats, r...

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Autores principales:	Teruyo Kida, Hidehiro Oku, Sho Osuka, Taeko Horie, Tsunehiko Ikeda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/957f5abe07324e768c6d21ba5ea03559
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spelling	oai:doaj.org-article:957f5abe07324e768c6d21ba5ea035592021-12-02T13:56:47ZHyperglycemia-induced VEGF and ROS production in retinal cells is inhibited by the mTOR inhibitor, rapamycin10.1038/s41598-021-81482-32045-2322https://doaj.org/article/957f5abe07324e768c6d21ba5ea035592021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81482-3https://doaj.org/toc/2045-2322Abstract Determine the impact of the mTOR inhibitor, rapamycin, on the hyperglycemia-induced expression of vascular endothelial growth factor (VEGF) and the production of reactive oxygen species (ROS) in retinal cells. Rats made hyperglycemic for 8 weeks by streptozotocin, as well as control rats, received i.p. rapamycin (1 mg/kg) for 3 days prior to immunostaining of their retinas with anti-VEGF and anti-glial fibrillary acidic protein (GFAP) and measuring retinal protein levels of VEGF and GFAP by Western blotting. In other experiments, flow cytometry analysis of ethidium fluorescence determined intracellular ROS levels in the absence or presence of rapamycin (1 μM) under normoglycemic (5.5 mM) and hyperglycemic (25 mM) conditions in a rat retinal Müller cell line (TR-MUL5) and primary human retinal microvascular endothelial cells (HRMECs). In the diabetic retina, VEGF was elevated and colocalized with the glial marker, GFAP, whose level was also elevated. Treatment with rapamycin inhibited the diabetes-induced VEGF and GFAP increases. We also found that raising extracellular glucose from 5.5 mM to 25 mM resulted in significant rapamycin-sensitive increases in the ROS levels of TR-MUL5 cells and HRMECs. In rat retina, rapamycin attenuates the diabetes-induced VEGF overexpression, and in cultured Müller cells and HRMECs, inhibits the hyperglycemia-induced boost ROS.Teruyo KidaHidehiro OkuSho OsukaTaeko HorieTsunehiko IkedaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Teruyo Kida Hidehiro Oku Sho Osuka Taeko Horie Tsunehiko Ikeda Hyperglycemia-induced VEGF and ROS production in retinal cells is inhibited by the mTOR inhibitor, rapamycin
description	Abstract Determine the impact of the mTOR inhibitor, rapamycin, on the hyperglycemia-induced expression of vascular endothelial growth factor (VEGF) and the production of reactive oxygen species (ROS) in retinal cells. Rats made hyperglycemic for 8 weeks by streptozotocin, as well as control rats, received i.p. rapamycin (1 mg/kg) for 3 days prior to immunostaining of their retinas with anti-VEGF and anti-glial fibrillary acidic protein (GFAP) and measuring retinal protein levels of VEGF and GFAP by Western blotting. In other experiments, flow cytometry analysis of ethidium fluorescence determined intracellular ROS levels in the absence or presence of rapamycin (1 μM) under normoglycemic (5.5 mM) and hyperglycemic (25 mM) conditions in a rat retinal Müller cell line (TR-MUL5) and primary human retinal microvascular endothelial cells (HRMECs). In the diabetic retina, VEGF was elevated and colocalized with the glial marker, GFAP, whose level was also elevated. Treatment with rapamycin inhibited the diabetes-induced VEGF and GFAP increases. We also found that raising extracellular glucose from 5.5 mM to 25 mM resulted in significant rapamycin-sensitive increases in the ROS levels of TR-MUL5 cells and HRMECs. In rat retina, rapamycin attenuates the diabetes-induced VEGF overexpression, and in cultured Müller cells and HRMECs, inhibits the hyperglycemia-induced boost ROS.
format	article
author	Teruyo Kida Hidehiro Oku Sho Osuka Taeko Horie Tsunehiko Ikeda
author_facet	Teruyo Kida Hidehiro Oku Sho Osuka Taeko Horie Tsunehiko Ikeda
author_sort	Teruyo Kida
title	Hyperglycemia-induced VEGF and ROS production in retinal cells is inhibited by the mTOR inhibitor, rapamycin
title_short	Hyperglycemia-induced VEGF and ROS production in retinal cells is inhibited by the mTOR inhibitor, rapamycin
title_full	Hyperglycemia-induced VEGF and ROS production in retinal cells is inhibited by the mTOR inhibitor, rapamycin
title_fullStr	Hyperglycemia-induced VEGF and ROS production in retinal cells is inhibited by the mTOR inhibitor, rapamycin
title_full_unstemmed	Hyperglycemia-induced VEGF and ROS production in retinal cells is inhibited by the mTOR inhibitor, rapamycin
title_sort	hyperglycemia-induced vegf and ros production in retinal cells is inhibited by the mtor inhibitor, rapamycin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/957f5abe07324e768c6d21ba5ea03559
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Hyperglycemia-induced VEGF and ROS production in retinal cells is inhibited by the mTOR inhibitor, rapamycin

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