Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model

Kota Sato; Atsunobu Takeda; Eiichi Hasegawa; Young Joon Jo; Mitsuru Arima; Yuji Oshima; Yanai Ryoji; Toru Nakazawa; Mitsuko Yuzawa; Hiroyuki Nakashizuka; Hiroyuki Shimada; Kazuhiro Kimura; Tatsuro Ishibashi; Koh Hei Sonoda

doi:10.1080/09114300.2018.1451609

Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model

Kota Sato, Atsunobu Takeda, Eiichi Hasegawa, Young Joon Jo, Mitsuru Arima, Yuji Oshima, Yanai Ryoji, Toru Nakazawa, Mitsuko Yuzawa, Hiroyuki Nakashizuka, Hiroyuki Shimada, Kazuhiro Kimura, Tatsuro Ishibashi, Koh Hei Sonoda

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10 Citations (Scopus)

Abstract

Subretinal fibrosis has been recognized as a feature of an advanced stage of exudative age-related macular degeneration (AMD) that leads to irreversible loss of vision. This study was aimed at elucidating roles of interlukin-6 (IL-6) in the development of subretinal fibrosis. Immunohistochemistry (IHC) was performed with anti-human IL-6 antibody in surgically excised choroidal neovascular tissues from patients with exudative AMD. The area of subretinal fibrosis was measured in a mouse subretinal fibrosis model with injection of control small interfering RNA(siRNA) or IL-6 siRNA, or isotype control antibody or anti-IL-6 receptor antibody after peritoneal exudative cells (PECs) injection into the vitreous cavity. PECs derived from IL-6 ^+/+ or IL-6 ^−∕− mice were placed into the subretinal space of IL-6 ^+/+ mice. IL-6 was expressed in the stroma and retinal pigment epithelial (RPE) layer in the choroidal neovascular tissues. IL-6 knockdown or blocking of the IL-6 receptor suppressed the formation of subretinal fibroblastic scars. The area of subretinal fibrosis induced by PECs derived from IL-6 ^−∕− mice was less than that induced by PECs from IL-6 ^+/+ mice. The results suggested that IL-6, expressed by activated macrophages, is a crucial mediator that promotes subretinal fibrosis. Targeting IL-6 and the corresponding signaling pathway would be an attractive therapeutic approach not only in choroidal neovascularization, but also in subretinal fibrosis.

Original language	English
Pages (from-to)	23-29
Number of pages	7
Journal	Immunological Medicine
Volume	41
Issue number	1
DOIs	https://doi.org/10.1080/09114300.2018.1451609
Publication status	Published - 2018 Jan 2

Keywords

Macrophage
age-related macular degeneration
interleukin-6
retinal pigment epithelial cells
subretinal fibrosis

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1080/09114300.2018.1451609

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@article{3484d24da9e14a72aaec5f63ecaabcc2,

title = "Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model",

abstract = " Subretinal fibrosis has been recognized as a feature of an advanced stage of exudative age-related macular degeneration (AMD) that leads to irreversible loss of vision. This study was aimed at elucidating roles of interlukin-6 (IL-6) in the development of subretinal fibrosis. Immunohistochemistry (IHC) was performed with anti-human IL-6 antibody in surgically excised choroidal neovascular tissues from patients with exudative AMD. The area of subretinal fibrosis was measured in a mouse subretinal fibrosis model with injection of control small interfering RNA(siRNA) or IL-6 siRNA, or isotype control antibody or anti-IL-6 receptor antibody after peritoneal exudative cells (PECs) injection into the vitreous cavity. PECs derived from IL-6 +/+ or IL-6 −∕− mice were placed into the subretinal space of IL-6 +/+ mice. IL-6 was expressed in the stroma and retinal pigment epithelial (RPE) layer in the choroidal neovascular tissues. IL-6 knockdown or blocking of the IL-6 receptor suppressed the formation of subretinal fibroblastic scars. The area of subretinal fibrosis induced by PECs derived from IL-6 −∕− mice was less than that induced by PECs from IL-6 +/+ mice. The results suggested that IL-6, expressed by activated macrophages, is a crucial mediator that promotes subretinal fibrosis. Targeting IL-6 and the corresponding signaling pathway would be an attractive therapeutic approach not only in choroidal neovascularization, but also in subretinal fibrosis. ",

keywords = "Macrophage, age-related macular degeneration, interleukin-6, retinal pigment epithelial cells, subretinal fibrosis",

author = "Kota Sato and Atsunobu Takeda and Eiichi Hasegawa and Jo, {Young Joon} and Mitsuru Arima and Yuji Oshima and Yanai Ryoji and Toru Nakazawa and Mitsuko Yuzawa and Hiroyuki Nakashizuka and Hiroyuki Shimada and Kazuhiro Kimura and Tatsuro Ishibashi and Sonoda, {Koh Hei}",

note = "Funding Information: This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI [15K10896] (grants C to AT) and Grant Number [10294943] [grants B (K-H.S.)] from the Ministry of Education, Science, Sports and Culture, Japan. Publisher Copyright: {\textcopyright} 2018, {\textcopyright} 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Japanese Society of Clinical Immunology.",

year = "2018",

month = jan,

day = "2",

doi = "10.1080/09114300.2018.1451609",

language = "English",

volume = "41",

pages = "23--29",

journal = "Immunological Medicine",

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T1 - Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model

AU - Sato, Kota

AU - Takeda, Atsunobu

AU - Hasegawa, Eiichi

AU - Jo, Young Joon

AU - Arima, Mitsuru

AU - Oshima, Yuji

AU - Ryoji, Yanai

AU - Nakazawa, Toru

AU - Yuzawa, Mitsuko

AU - Nakashizuka, Hiroyuki

AU - Shimada, Hiroyuki

AU - Kimura, Kazuhiro

AU - Ishibashi, Tatsuro

AU - Sonoda, Koh Hei

N1 - Funding Information: This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI [15K10896] (grants C to AT) and Grant Number [10294943] [grants B (K-H.S.)] from the Ministry of Education, Science, Sports and Culture, Japan. Publisher Copyright: © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Japanese Society of Clinical Immunology.

PY - 2018/1/2

Y1 - 2018/1/2

N2 - Subretinal fibrosis has been recognized as a feature of an advanced stage of exudative age-related macular degeneration (AMD) that leads to irreversible loss of vision. This study was aimed at elucidating roles of interlukin-6 (IL-6) in the development of subretinal fibrosis. Immunohistochemistry (IHC) was performed with anti-human IL-6 antibody in surgically excised choroidal neovascular tissues from patients with exudative AMD. The area of subretinal fibrosis was measured in a mouse subretinal fibrosis model with injection of control small interfering RNA(siRNA) or IL-6 siRNA, or isotype control antibody or anti-IL-6 receptor antibody after peritoneal exudative cells (PECs) injection into the vitreous cavity. PECs derived from IL-6 +/+ or IL-6 −∕− mice were placed into the subretinal space of IL-6 +/+ mice. IL-6 was expressed in the stroma and retinal pigment epithelial (RPE) layer in the choroidal neovascular tissues. IL-6 knockdown or blocking of the IL-6 receptor suppressed the formation of subretinal fibroblastic scars. The area of subretinal fibrosis induced by PECs derived from IL-6 −∕− mice was less than that induced by PECs from IL-6 +/+ mice. The results suggested that IL-6, expressed by activated macrophages, is a crucial mediator that promotes subretinal fibrosis. Targeting IL-6 and the corresponding signaling pathway would be an attractive therapeutic approach not only in choroidal neovascularization, but also in subretinal fibrosis.

AB - Subretinal fibrosis has been recognized as a feature of an advanced stage of exudative age-related macular degeneration (AMD) that leads to irreversible loss of vision. This study was aimed at elucidating roles of interlukin-6 (IL-6) in the development of subretinal fibrosis. Immunohistochemistry (IHC) was performed with anti-human IL-6 antibody in surgically excised choroidal neovascular tissues from patients with exudative AMD. The area of subretinal fibrosis was measured in a mouse subretinal fibrosis model with injection of control small interfering RNA(siRNA) or IL-6 siRNA, or isotype control antibody or anti-IL-6 receptor antibody after peritoneal exudative cells (PECs) injection into the vitreous cavity. PECs derived from IL-6 +/+ or IL-6 −∕− mice were placed into the subretinal space of IL-6 +/+ mice. IL-6 was expressed in the stroma and retinal pigment epithelial (RPE) layer in the choroidal neovascular tissues. IL-6 knockdown or blocking of the IL-6 receptor suppressed the formation of subretinal fibroblastic scars. The area of subretinal fibrosis induced by PECs derived from IL-6 −∕− mice was less than that induced by PECs from IL-6 +/+ mice. The results suggested that IL-6, expressed by activated macrophages, is a crucial mediator that promotes subretinal fibrosis. Targeting IL-6 and the corresponding signaling pathway would be an attractive therapeutic approach not only in choroidal neovascularization, but also in subretinal fibrosis.

KW - Macrophage

KW - age-related macular degeneration

KW - interleukin-6

KW - retinal pigment epithelial cells

KW - subretinal fibrosis

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JO - Immunological Medicine

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Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model

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Keywords

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