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Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia

Visual function depends on the intimate structural, functional and metabolic interactions between the retinal pigment epithelium (RPE) and the neural retina. The daily phagocytosis of the photoreceptor outer segment tips by the overlaying RPE provides essential nutrients for the RPE itself and photo...

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Autores principales: Dhingra, Anuradha, Sharp, Rachel C., Kim, Taewan, Popov, Anatoliy V., Ying, Gui-Shuang, Pietrofesa, Ralph A., Park, Kyewon, Christofidou-Solomidou, Melpo, Boesze-Battaglia, Kathleen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198017/
https://www.ncbi.nlm.nih.gov/pubmed/34071220
http://dx.doi.org/10.3390/ijms22115764
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author Dhingra, Anuradha
Sharp, Rachel C.
Kim, Taewan
Popov, Anatoliy V.
Ying, Gui-Shuang
Pietrofesa, Ralph A.
Park, Kyewon
Christofidou-Solomidou, Melpo
Boesze-Battaglia, Kathleen
author_facet Dhingra, Anuradha
Sharp, Rachel C.
Kim, Taewan
Popov, Anatoliy V.
Ying, Gui-Shuang
Pietrofesa, Ralph A.
Park, Kyewon
Christofidou-Solomidou, Melpo
Boesze-Battaglia, Kathleen
author_sort Dhingra, Anuradha
collection PubMed
description Visual function depends on the intimate structural, functional and metabolic interactions between the retinal pigment epithelium (RPE) and the neural retina. The daily phagocytosis of the photoreceptor outer segment tips by the overlaying RPE provides essential nutrients for the RPE itself and photoreceptors through intricate metabolic synergy. Age-related retinal changes are often characterized by metabolic dysregulation contributing to increased lipid accumulation and peroxidation as well as the release of proinflammatory cytokines. LGM2605 is a synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant and anti-inflammatory properties demonstrated in diverse in vitro and in vivo inflammatory disease models. In these studies, we tested the hypothesis that LGM2605 may be an attractive small-scale therapeutic that protects RPE against inflammation and restores its metabolic capacity under lipid overload. Using an in vitro model in which loss of the autophagy protein, LC3B, results in defective phagosome degradation and metabolic dysregulation, we show that lipid overload results in increased gasdermin cleavage, IL-1 β release, lipid accumulation and decreased oxidative capacity. The addition of LGM2605 resulted in enhanced mitochondrial capacity, decreased lipid accumulation and amelioration of IL-1 β release in a model of defective lipid homeostasis. Collectively, these studies suggest that lipid overload decreases mitochondrial function and increases the inflammatory response, with LGM2605 acting as a protective agent.
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spelling pubmed-81980172021-06-14 Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia Dhingra, Anuradha Sharp, Rachel C. Kim, Taewan Popov, Anatoliy V. Ying, Gui-Shuang Pietrofesa, Ralph A. Park, Kyewon Christofidou-Solomidou, Melpo Boesze-Battaglia, Kathleen Int J Mol Sci Article Visual function depends on the intimate structural, functional and metabolic interactions between the retinal pigment epithelium (RPE) and the neural retina. The daily phagocytosis of the photoreceptor outer segment tips by the overlaying RPE provides essential nutrients for the RPE itself and photoreceptors through intricate metabolic synergy. Age-related retinal changes are often characterized by metabolic dysregulation contributing to increased lipid accumulation and peroxidation as well as the release of proinflammatory cytokines. LGM2605 is a synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant and anti-inflammatory properties demonstrated in diverse in vitro and in vivo inflammatory disease models. In these studies, we tested the hypothesis that LGM2605 may be an attractive small-scale therapeutic that protects RPE against inflammation and restores its metabolic capacity under lipid overload. Using an in vitro model in which loss of the autophagy protein, LC3B, results in defective phagosome degradation and metabolic dysregulation, we show that lipid overload results in increased gasdermin cleavage, IL-1 β release, lipid accumulation and decreased oxidative capacity. The addition of LGM2605 resulted in enhanced mitochondrial capacity, decreased lipid accumulation and amelioration of IL-1 β release in a model of defective lipid homeostasis. Collectively, these studies suggest that lipid overload decreases mitochondrial function and increases the inflammatory response, with LGM2605 acting as a protective agent. MDPI 2021-05-28 /pmc/articles/PMC8198017/ /pubmed/34071220 http://dx.doi.org/10.3390/ijms22115764 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
Dhingra, Anuradha
Sharp, Rachel C.
Kim, Taewan
Popov, Anatoliy V.
Ying, Gui-Shuang
Pietrofesa, Ralph A.
Park, Kyewon
Christofidou-Solomidou, Melpo
Boesze-Battaglia, Kathleen
Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia
title Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia
title_full Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia
title_fullStr Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia
title_full_unstemmed Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia
title_short Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia
title_sort assessment of a small molecule synthetic lignan in enhancing oxidative balance and decreasing lipid accumulation in human retinal pigment epithelia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198017/
https://www.ncbi.nlm.nih.gov/pubmed/34071220
http://dx.doi.org/10.3390/ijms22115764
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