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Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway

Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium i...

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Autores principales: Chang, Yuan-Yen, Lee, Yi-Ju, Hsu, Min-Yen, Wang, Meilin, Tsou, Shang-Chun, Chen, Ching-Chung, Lin, Jer-An, Hsiao, Yai-Ping, Lin, Hui-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071060/
https://www.ncbi.nlm.nih.gov/pubmed/33919990
http://dx.doi.org/10.3390/ijms22084056
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author Chang, Yuan-Yen
Lee, Yi-Ju
Hsu, Min-Yen
Wang, Meilin
Tsou, Shang-Chun
Chen, Ching-Chung
Lin, Jer-An
Hsiao, Yai-Ping
Lin, Hui-Wen
author_facet Chang, Yuan-Yen
Lee, Yi-Ju
Hsu, Min-Yen
Wang, Meilin
Tsou, Shang-Chun
Chen, Ching-Chung
Lin, Jer-An
Hsiao, Yai-Ping
Lin, Hui-Wen
author_sort Chang, Yuan-Yen
collection PubMed
description Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO(3)) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO(3)-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO(3)-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO(3)-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO(3)-mediated apoptosis.
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spelling pubmed-80710602021-04-26 Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway Chang, Yuan-Yen Lee, Yi-Ju Hsu, Min-Yen Wang, Meilin Tsou, Shang-Chun Chen, Ching-Chung Lin, Jer-An Hsiao, Yai-Ping Lin, Hui-Wen Int J Mol Sci Article Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO(3)) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO(3)-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO(3)-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO(3)-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO(3)-mediated apoptosis. MDPI 2021-04-14 /pmc/articles/PMC8071060/ /pubmed/33919990 http://dx.doi.org/10.3390/ijms22084056 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Yuan-Yen
Lee, Yi-Ju
Hsu, Min-Yen
Wang, Meilin
Tsou, Shang-Chun
Chen, Ching-Chung
Lin, Jer-An
Hsiao, Yai-Ping
Lin, Hui-Wen
Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway
title Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway
title_full Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway
title_fullStr Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway
title_full_unstemmed Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway
title_short Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway
title_sort protective effect of quercetin on sodium iodate-induced retinal apoptosis through the reactive oxygen species-mediated mitochondrion-dependent pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071060/
https://www.ncbi.nlm.nih.gov/pubmed/33919990
http://dx.doi.org/10.3390/ijms22084056
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