Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization
Abstract Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signal...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Lückoff, Anika [verfasserIn] Caramoy, Albert [verfasserIn] Scholz, Rebecca [verfasserIn] Prinz, Marco [verfasserIn] Kalinke, Ulrich [verfasserIn] Langmann, Thomas [verfasserIn] |
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E-Artikel |
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Englisch |
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2016 |
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© The Authors. Published under the terms of the CC BY 4.0 license 2016 |
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| Übergeordnetes Werk: |
Enthalten in: EMBO Molecular Medicine - Nature Publishing Group UK, 2023, 8(2016), 6 vom: 03. Mai, Seite 670-678 |
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| Übergeordnetes Werk: |
volume:8 ; year:2016 ; number:6 ; day:03 ; month:05 ; pages:670-678 |
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| DOI / URN: |
10.15252/emmm.201505994 |
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| Katalog-ID: |
SPR057908028 |
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| 245 | 1 | 0 | |a Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization |
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| 520 | |a Abstract Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon‐α/β receptor (Ifnar) using Ifnar$ 1^{−/−} $ mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser‐treated Cx3cr1CreER:Ifnar1fl/fl animals that allowed the tamoxifen‐induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN‐β therapy of laser‐treated wild‐type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN‐β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. | ||
| 520 | |a Synopsis Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. Loss of Ifnar1 signaling triggers retinal microglia and macrophage reactivity and promotes angiogenesis in a laser‐induced model for AMD.Specific knockdown of Ifnar1 in mononuclear phagocytes affects their immunomodulatory potential and exacerbates choroidal neovascularization.IFN‐β therapy attenuates microgliosis and macrophage reactivity and thereby reduces choroidal neovascularization. | ||
| 520 | |a Graphical Abstract Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. | ||
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| 650 | 4 | |a choroidal neovascularization |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a interferon‐beta signaling |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a macrophages |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a microglia |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Caramoy, Albert |e verfasserin |4 aut | |
| 700 | 1 | |a Scholz, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Prinz, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Kalinke, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Langmann, Thomas |e verfasserin |0 (orcid)0000-0001-6826-529X |4 aut | |
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10.15252/emmm.201505994 doi (DE-627)SPR057908028 (SPR)emmm.201505994-e DE-627 ger DE-627 rakwb eng Lückoff, Anika verfasserin aut Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2016 Abstract Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon‐α/β receptor (Ifnar) using Ifnar$ 1^{−/−} $ mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser‐treated Cx3cr1CreER:Ifnar1fl/fl animals that allowed the tamoxifen‐induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN‐β therapy of laser‐treated wild‐type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN‐β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. Synopsis Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. Loss of Ifnar1 signaling triggers retinal microglia and macrophage reactivity and promotes angiogenesis in a laser‐induced model for AMD.Specific knockdown of Ifnar1 in mononuclear phagocytes affects their immunomodulatory potential and exacerbates choroidal neovascularization.IFN‐β therapy attenuates microgliosis and macrophage reactivity and thereby reduces choroidal neovascularization. Graphical Abstract Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. age‐related macular degeneration (dpeaa)DE-He213 choroidal neovascularization (dpeaa)DE-He213 interferon‐beta signaling (dpeaa)DE-He213 macrophages (dpeaa)DE-He213 microglia (dpeaa)DE-He213 Caramoy, Albert verfasserin aut Scholz, Rebecca verfasserin aut Prinz, Marco verfasserin aut Kalinke, Ulrich verfasserin aut Langmann, Thomas verfasserin (orcid)0000-0001-6826-529X aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 8(2016), 6 vom: 03. Mai, Seite 670-678 (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:8 year:2016 number:6 day:03 month:05 pages:670-678 https://dx.doi.org/10.15252/emmm.201505994 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 8 2016 6 03 05 670-678 |
| spelling |
10.15252/emmm.201505994 doi (DE-627)SPR057908028 (SPR)emmm.201505994-e DE-627 ger DE-627 rakwb eng Lückoff, Anika verfasserin aut Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2016 Abstract Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon‐α/β receptor (Ifnar) using Ifnar$ 1^{−/−} $ mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser‐treated Cx3cr1CreER:Ifnar1fl/fl animals that allowed the tamoxifen‐induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN‐β therapy of laser‐treated wild‐type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN‐β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. Synopsis Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. Loss of Ifnar1 signaling triggers retinal microglia and macrophage reactivity and promotes angiogenesis in a laser‐induced model for AMD.Specific knockdown of Ifnar1 in mononuclear phagocytes affects their immunomodulatory potential and exacerbates choroidal neovascularization.IFN‐β therapy attenuates microgliosis and macrophage reactivity and thereby reduces choroidal neovascularization. Graphical Abstract Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. age‐related macular degeneration (dpeaa)DE-He213 choroidal neovascularization (dpeaa)DE-He213 interferon‐beta signaling (dpeaa)DE-He213 macrophages (dpeaa)DE-He213 microglia (dpeaa)DE-He213 Caramoy, Albert verfasserin aut Scholz, Rebecca verfasserin aut Prinz, Marco verfasserin aut Kalinke, Ulrich verfasserin aut Langmann, Thomas verfasserin (orcid)0000-0001-6826-529X aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 8(2016), 6 vom: 03. Mai, Seite 670-678 (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:8 year:2016 number:6 day:03 month:05 pages:670-678 https://dx.doi.org/10.15252/emmm.201505994 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 8 2016 6 03 05 670-678 |
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10.15252/emmm.201505994 doi (DE-627)SPR057908028 (SPR)emmm.201505994-e DE-627 ger DE-627 rakwb eng Lückoff, Anika verfasserin aut Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2016 Abstract Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon‐α/β receptor (Ifnar) using Ifnar$ 1^{−/−} $ mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser‐treated Cx3cr1CreER:Ifnar1fl/fl animals that allowed the tamoxifen‐induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN‐β therapy of laser‐treated wild‐type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN‐β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. Synopsis Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. Loss of Ifnar1 signaling triggers retinal microglia and macrophage reactivity and promotes angiogenesis in a laser‐induced model for AMD.Specific knockdown of Ifnar1 in mononuclear phagocytes affects their immunomodulatory potential and exacerbates choroidal neovascularization.IFN‐β therapy attenuates microgliosis and macrophage reactivity and thereby reduces choroidal neovascularization. Graphical Abstract Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. age‐related macular degeneration (dpeaa)DE-He213 choroidal neovascularization (dpeaa)DE-He213 interferon‐beta signaling (dpeaa)DE-He213 macrophages (dpeaa)DE-He213 microglia (dpeaa)DE-He213 Caramoy, Albert verfasserin aut Scholz, Rebecca verfasserin aut Prinz, Marco verfasserin aut Kalinke, Ulrich verfasserin aut Langmann, Thomas verfasserin (orcid)0000-0001-6826-529X aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 8(2016), 6 vom: 03. Mai, Seite 670-678 (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:8 year:2016 number:6 day:03 month:05 pages:670-678 https://dx.doi.org/10.15252/emmm.201505994 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 8 2016 6 03 05 670-678 |
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10.15252/emmm.201505994 doi (DE-627)SPR057908028 (SPR)emmm.201505994-e DE-627 ger DE-627 rakwb eng Lückoff, Anika verfasserin aut Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2016 Abstract Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon‐α/β receptor (Ifnar) using Ifnar$ 1^{−/−} $ mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser‐treated Cx3cr1CreER:Ifnar1fl/fl animals that allowed the tamoxifen‐induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN‐β therapy of laser‐treated wild‐type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN‐β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. Synopsis Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. Loss of Ifnar1 signaling triggers retinal microglia and macrophage reactivity and promotes angiogenesis in a laser‐induced model for AMD.Specific knockdown of Ifnar1 in mononuclear phagocytes affects their immunomodulatory potential and exacerbates choroidal neovascularization.IFN‐β therapy attenuates microgliosis and macrophage reactivity and thereby reduces choroidal neovascularization. Graphical Abstract Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. age‐related macular degeneration (dpeaa)DE-He213 choroidal neovascularization (dpeaa)DE-He213 interferon‐beta signaling (dpeaa)DE-He213 macrophages (dpeaa)DE-He213 microglia (dpeaa)DE-He213 Caramoy, Albert verfasserin aut Scholz, Rebecca verfasserin aut Prinz, Marco verfasserin aut Kalinke, Ulrich verfasserin aut Langmann, Thomas verfasserin (orcid)0000-0001-6826-529X aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 8(2016), 6 vom: 03. Mai, Seite 670-678 (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:8 year:2016 number:6 day:03 month:05 pages:670-678 https://dx.doi.org/10.15252/emmm.201505994 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 8 2016 6 03 05 670-678 |
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10.15252/emmm.201505994 doi (DE-627)SPR057908028 (SPR)emmm.201505994-e DE-627 ger DE-627 rakwb eng Lückoff, Anika verfasserin aut Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2016 Abstract Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon‐α/β receptor (Ifnar) using Ifnar$ 1^{−/−} $ mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser‐treated Cx3cr1CreER:Ifnar1fl/fl animals that allowed the tamoxifen‐induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN‐β therapy of laser‐treated wild‐type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN‐β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. Synopsis Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. Loss of Ifnar1 signaling triggers retinal microglia and macrophage reactivity and promotes angiogenesis in a laser‐induced model for AMD.Specific knockdown of Ifnar1 in mononuclear phagocytes affects their immunomodulatory potential and exacerbates choroidal neovascularization.IFN‐β therapy attenuates microgliosis and macrophage reactivity and thereby reduces choroidal neovascularization. Graphical Abstract Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. age‐related macular degeneration (dpeaa)DE-He213 choroidal neovascularization (dpeaa)DE-He213 interferon‐beta signaling (dpeaa)DE-He213 macrophages (dpeaa)DE-He213 microglia (dpeaa)DE-He213 Caramoy, Albert verfasserin aut Scholz, Rebecca verfasserin aut Prinz, Marco verfasserin aut Kalinke, Ulrich verfasserin aut Langmann, Thomas verfasserin (orcid)0000-0001-6826-529X aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 8(2016), 6 vom: 03. Mai, Seite 670-678 (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:8 year:2016 number:6 day:03 month:05 pages:670-678 https://dx.doi.org/10.15252/emmm.201505994 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 8 2016 6 03 05 670-678 |
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Lückoff, Anika |
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Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization age‐related macular degeneration (dpeaa)DE-He213 choroidal neovascularization (dpeaa)DE-He213 interferon‐beta signaling (dpeaa)DE-He213 macrophages (dpeaa)DE-He213 microglia (dpeaa)DE-He213 |
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interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization |
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Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization |
| abstract |
Abstract Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon‐α/β receptor (Ifnar) using Ifnar$ 1^{−/−} $ mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser‐treated Cx3cr1CreER:Ifnar1fl/fl animals that allowed the tamoxifen‐induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN‐β therapy of laser‐treated wild‐type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN‐β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. Synopsis Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. Loss of Ifnar1 signaling triggers retinal microglia and macrophage reactivity and promotes angiogenesis in a laser‐induced model for AMD.Specific knockdown of Ifnar1 in mononuclear phagocytes affects their immunomodulatory potential and exacerbates choroidal neovascularization.IFN‐β therapy attenuates microgliosis and macrophage reactivity and thereby reduces choroidal neovascularization. Graphical Abstract Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. © The Authors. Published under the terms of the CC BY 4.0 license 2016 |
| abstractGer |
Abstract Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon‐α/β receptor (Ifnar) using Ifnar$ 1^{−/−} $ mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser‐treated Cx3cr1CreER:Ifnar1fl/fl animals that allowed the tamoxifen‐induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN‐β therapy of laser‐treated wild‐type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN‐β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. Synopsis Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. Loss of Ifnar1 signaling triggers retinal microglia and macrophage reactivity and promotes angiogenesis in a laser‐induced model for AMD.Specific knockdown of Ifnar1 in mononuclear phagocytes affects their immunomodulatory potential and exacerbates choroidal neovascularization.IFN‐β therapy attenuates microgliosis and macrophage reactivity and thereby reduces choroidal neovascularization. Graphical Abstract Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. © The Authors. Published under the terms of the CC BY 4.0 license 2016 |
| abstract_unstemmed |
Abstract Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon‐α/β receptor (Ifnar) using Ifnar$ 1^{−/−} $ mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser‐treated Cx3cr1CreER:Ifnar1fl/fl animals that allowed the tamoxifen‐induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN‐β therapy of laser‐treated wild‐type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN‐β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. Synopsis Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. Loss of Ifnar1 signaling triggers retinal microglia and macrophage reactivity and promotes angiogenesis in a laser‐induced model for AMD.Specific knockdown of Ifnar1 in mononuclear phagocytes affects their immunomodulatory potential and exacerbates choroidal neovascularization.IFN‐β therapy attenuates microgliosis and macrophage reactivity and thereby reduces choroidal neovascularization. Graphical Abstract Innate immune activation is a hallmark of age‐related macular degeneration (AMD). Here, interferon‐beta signaling was identified as an intrinsic regulator of retinal mononuclear phagocytes and therefore as potential therapeutic target for AMD. © The Authors. Published under the terms of the CC BY 4.0 license 2016 |
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Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization |
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Caramoy, Albert Scholz, Rebecca Prinz, Marco Kalinke, Ulrich Langmann, Thomas |
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