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Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis
Neovascular age-related macular degeneration (nAMD) commonly causes vision loss from aberrant angiogenesis, termed choroidal neovascularization (CNV). Interleukin-6 (IL6) is a pro-inflammatory and pro-angiogenic cytokine that is correlated with AMD progression and nAMD activity. We hypothesize that...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433398/ https://www.ncbi.nlm.nih.gov/pubmed/34508129 http://dx.doi.org/10.1038/s41598-021-97522-x |
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author | Droho, Steven Cuda, Carla M. Perlman, Harris Lavine, Jeremy A. |
author_facet | Droho, Steven Cuda, Carla M. Perlman, Harris Lavine, Jeremy A. |
author_sort | Droho, Steven |
collection | PubMed |
description | Neovascular age-related macular degeneration (nAMD) commonly causes vision loss from aberrant angiogenesis, termed choroidal neovascularization (CNV). Interleukin-6 (IL6) is a pro-inflammatory and pro-angiogenic cytokine that is correlated with AMD progression and nAMD activity. We hypothesize that anti-IL6 therapy is a potential nAMD therapeutic. We found that IL6 levels were increased after laser injury and expressed by macrophages. Il6-deficiency decreased laser-induced CNV area and exogenous IL6 addition increased choroidal sprouting angiogenesis. Il6-null mice demonstrated equally increased macrophage numbers as wildtype mice. At steady state, IL6R expression was detected on peripheral blood and ocular monocytes. After laser injury, the number of IL6R(+)Ly6C(+) monocytes in blood and IL6R(+) macrophages in the eye were increased. In human choroid, macrophages expressed IL6, IL6R, and IL6ST. Furthermore, IL6R(+) macrophages displayed a transcriptional profile consistent with STAT3 (signal transducer and activator of transcription 3) activation and angiogenesis. Our data show that IL6 is both necessary and sufficient for choroidal angiogenesis. Macrophage-derived IL6 may stimulate choroidal angiogenesis via classical activation of IL6R(+) macrophages, which then stimulate angiogenesis. Targeting IL6 or the IL6R could be an effective adjunctive therapy for treatment-resistant nAMD patients. |
format | Online Article Text |
id | pubmed-8433398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84333982021-09-13 Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis Droho, Steven Cuda, Carla M. Perlman, Harris Lavine, Jeremy A. Sci Rep Article Neovascular age-related macular degeneration (nAMD) commonly causes vision loss from aberrant angiogenesis, termed choroidal neovascularization (CNV). Interleukin-6 (IL6) is a pro-inflammatory and pro-angiogenic cytokine that is correlated with AMD progression and nAMD activity. We hypothesize that anti-IL6 therapy is a potential nAMD therapeutic. We found that IL6 levels were increased after laser injury and expressed by macrophages. Il6-deficiency decreased laser-induced CNV area and exogenous IL6 addition increased choroidal sprouting angiogenesis. Il6-null mice demonstrated equally increased macrophage numbers as wildtype mice. At steady state, IL6R expression was detected on peripheral blood and ocular monocytes. After laser injury, the number of IL6R(+)Ly6C(+) monocytes in blood and IL6R(+) macrophages in the eye were increased. In human choroid, macrophages expressed IL6, IL6R, and IL6ST. Furthermore, IL6R(+) macrophages displayed a transcriptional profile consistent with STAT3 (signal transducer and activator of transcription 3) activation and angiogenesis. Our data show that IL6 is both necessary and sufficient for choroidal angiogenesis. Macrophage-derived IL6 may stimulate choroidal angiogenesis via classical activation of IL6R(+) macrophages, which then stimulate angiogenesis. Targeting IL6 or the IL6R could be an effective adjunctive therapy for treatment-resistant nAMD patients. Nature Publishing Group UK 2021-09-10 /pmc/articles/PMC8433398/ /pubmed/34508129 http://dx.doi.org/10.1038/s41598-021-97522-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Droho, Steven Cuda, Carla M. Perlman, Harris Lavine, Jeremy A. Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis |
title | Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis |
title_full | Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis |
title_fullStr | Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis |
title_full_unstemmed | Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis |
title_short | Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis |
title_sort | macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433398/ https://www.ncbi.nlm.nih.gov/pubmed/34508129 http://dx.doi.org/10.1038/s41598-021-97522-x |
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