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Resveratrol reverses the adverse effects of bevacizumab on cultured ARPE-19 cells

Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR) are one of the major causes of blindness caused by neo-vascular changes in the retina. Intravitreal anti-VEGF injections are widely used in the treatment of wet-AMD and PDR. A significant percentage of treated patien...

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Autores principales: Subramani, Murali, Ponnalagu, Murugeswari, Krishna, Lekshmi, Jeyabalan, Nallathambi, Chevour, Priyanka, Sharma, Anupam, Jayadev, Chaitra, Shetty, Rohit, Begum, Nargis, Archunan, Govindaraju, Das, Debashish
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612947/
https://www.ncbi.nlm.nih.gov/pubmed/28947815
http://dx.doi.org/10.1038/s41598-017-12496-z
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author Subramani, Murali
Ponnalagu, Murugeswari
Krishna, Lekshmi
Jeyabalan, Nallathambi
Chevour, Priyanka
Sharma, Anupam
Jayadev, Chaitra
Shetty, Rohit
Begum, Nargis
Archunan, Govindaraju
Das, Debashish
author_facet Subramani, Murali
Ponnalagu, Murugeswari
Krishna, Lekshmi
Jeyabalan, Nallathambi
Chevour, Priyanka
Sharma, Anupam
Jayadev, Chaitra
Shetty, Rohit
Begum, Nargis
Archunan, Govindaraju
Das, Debashish
author_sort Subramani, Murali
collection PubMed
description Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR) are one of the major causes of blindness caused by neo-vascular changes in the retina. Intravitreal anti-VEGF injections are widely used in the treatment of wet-AMD and PDR. A significant percentage of treated patients have complications of repeated injections. Resveratrol (RES) is a polyphenol phytoalexin with anti-oxidative, anti-inflammatory and anti-proliferative properties. Hence, we hypothesized that if RES is used in combination with bevacizumab (BEV, anti-VEGF), it could reverse the adverse effects that precipitate fibrotic changes, drusen formation, tractional retinal detachment and so on. Human retinal pigment epithelial cells were treated with various combinations of BEV and RES. There was partial reduction in secreted VEGF levels compared to untreated controls. Epithelial-mesenchymal transition was lower in BEV + RES treated cultures compared to BEV treated cultures. The proliferation status was similar in BEV + RES as well as BEV treated cultures both groups. Phagocytosis was enhanced in the presence of BEV + RES compared to BEV. Furthermore, we observed that notch signaling was involved in reversing the adverse effects of BEV. This study paves way for a combinatorial strategy to treat as well as prevent adverse effects of therapy in patients with wet AMD and PDR.
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spelling pubmed-56129472017-10-11 Resveratrol reverses the adverse effects of bevacizumab on cultured ARPE-19 cells Subramani, Murali Ponnalagu, Murugeswari Krishna, Lekshmi Jeyabalan, Nallathambi Chevour, Priyanka Sharma, Anupam Jayadev, Chaitra Shetty, Rohit Begum, Nargis Archunan, Govindaraju Das, Debashish Sci Rep Article Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR) are one of the major causes of blindness caused by neo-vascular changes in the retina. Intravitreal anti-VEGF injections are widely used in the treatment of wet-AMD and PDR. A significant percentage of treated patients have complications of repeated injections. Resveratrol (RES) is a polyphenol phytoalexin with anti-oxidative, anti-inflammatory and anti-proliferative properties. Hence, we hypothesized that if RES is used in combination with bevacizumab (BEV, anti-VEGF), it could reverse the adverse effects that precipitate fibrotic changes, drusen formation, tractional retinal detachment and so on. Human retinal pigment epithelial cells were treated with various combinations of BEV and RES. There was partial reduction in secreted VEGF levels compared to untreated controls. Epithelial-mesenchymal transition was lower in BEV + RES treated cultures compared to BEV treated cultures. The proliferation status was similar in BEV + RES as well as BEV treated cultures both groups. Phagocytosis was enhanced in the presence of BEV + RES compared to BEV. Furthermore, we observed that notch signaling was involved in reversing the adverse effects of BEV. This study paves way for a combinatorial strategy to treat as well as prevent adverse effects of therapy in patients with wet AMD and PDR. Nature Publishing Group UK 2017-09-25 /pmc/articles/PMC5612947/ /pubmed/28947815 http://dx.doi.org/10.1038/s41598-017-12496-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Subramani, Murali
Ponnalagu, Murugeswari
Krishna, Lekshmi
Jeyabalan, Nallathambi
Chevour, Priyanka
Sharma, Anupam
Jayadev, Chaitra
Shetty, Rohit
Begum, Nargis
Archunan, Govindaraju
Das, Debashish
Resveratrol reverses the adverse effects of bevacizumab on cultured ARPE-19 cells
title Resveratrol reverses the adverse effects of bevacizumab on cultured ARPE-19 cells
title_full Resveratrol reverses the adverse effects of bevacizumab on cultured ARPE-19 cells
title_fullStr Resveratrol reverses the adverse effects of bevacizumab on cultured ARPE-19 cells
title_full_unstemmed Resveratrol reverses the adverse effects of bevacizumab on cultured ARPE-19 cells
title_short Resveratrol reverses the adverse effects of bevacizumab on cultured ARPE-19 cells
title_sort resveratrol reverses the adverse effects of bevacizumab on cultured arpe-19 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612947/
https://www.ncbi.nlm.nih.gov/pubmed/28947815
http://dx.doi.org/10.1038/s41598-017-12496-z
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