TY - JOUR
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.
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U2 - 10.1080/09114300.2018.1451609
DO - 10.1080/09114300.2018.1451609
M3 - Article
C2 - 30938258
AN - SCOPUS:85050729717
VL - 41
SP - 23
EP - 29
JO - Immunological Medicine
JF - Immunological Medicine
SN - 0911-4300
IS - 1
ER -