Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis

Abstract 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 hypothes...

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Autores principales:	Steven Droho, Carla M. Cuda, Harris Perlman, Jeremy A. Lavine
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d584da551c324321991bcae9b2906845
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spelling	oai:doaj.org-article:d584da551c324321991bcae9b29068452021-12-02T17:19:16ZMacrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis10.1038/s41598-021-97522-x2045-2322https://doaj.org/article/d584da551c324321991bcae9b29068452021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97522-xhttps://doaj.org/toc/2045-2322Abstract 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.Steven DrohoCarla M. CudaHarris PerlmanJeremy A. LavineNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Steven Droho Carla M. Cuda Harris Perlman Jeremy A. Lavine Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis
description	Abstract 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	article
author	Steven Droho Carla M. Cuda Harris Perlman Jeremy A. Lavine
author_facet	Steven Droho Carla M. Cuda Harris Perlman Jeremy A. Lavine
author_sort	Steven Droho
title	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_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_sort	macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d584da551c324321991bcae9b2906845
work_keys_str_mv	AT stevendroho macrophagederivedinterleukin6isnecessaryandsufficientforchoroidalangiogenesis AT carlamcuda macrophagederivedinterleukin6isnecessaryandsufficientforchoroidalangiogenesis AT harrisperlman macrophagederivedinterleukin6isnecessaryandsufficientforchoroidalangiogenesis AT jeremyalavine macrophagederivedinterleukin6isnecessaryandsufficientforchoroidalangiogenesis
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Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis

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