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

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)23-29
Number of pages7
JournalImmunological Medicine
Volume41
Issue number1
DOIs
Publication statusPublished - Jan 2 2018

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Interleukin-6
Fibrosis
Macular Degeneration
Small Interfering RNA
Peritoneal Fibrosis
Choroidal Neovascularization
Injections
Retinal Pigments
Antibodies
Cicatrix
Anti-Idiotypic Antibodies
Immunohistochemistry
Macrophages
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model. / Sato, Kota; Takeda, Atsunobu; Hasegawa, Eiichi; Jo, Young Joon; Arima, Mitsuru; Oshima, Yuji; Ryoji, Yanai; Nakazawa, Toru; Yuzawa, Mitsuko; Nakashizuka, Hiroyuki; Shimada, Hiroyuki; Kimura, Kazuhiro; Ishibashi, Tatsuro; Sonoda, Koh Hei.

In: Immunological Medicine, Vol. 41, No. 1, 02.01.2018, p. 23-29.

Research output: Contribution to journalArticle

Sato, K, Takeda, A, Hasegawa, E, Jo, YJ, Arima, M, Oshima, Y, Ryoji, Y, Nakazawa, T, Yuzawa, M, Nakashizuka, H, Shimada, H, Kimura, K, Ishibashi, T & Sonoda, KH 2018, 'Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model', Immunological Medicine, vol. 41, no. 1, pp. 23-29. https://doi.org/10.1080/09114300.2018.1451609
Sato, Kota ; Takeda, Atsunobu ; Hasegawa, Eiichi ; Jo, Young Joon ; Arima, Mitsuru ; Oshima, Yuji ; Ryoji, Yanai ; Nakazawa, Toru ; Yuzawa, Mitsuko ; Nakashizuka, Hiroyuki ; Shimada, Hiroyuki ; Kimura, Kazuhiro ; Ishibashi, Tatsuro ; Sonoda, Koh Hei. / Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model. In: Immunological Medicine. 2018 ; Vol. 41, No. 1. pp. 23-29.
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AU - Nakashizuka, Hiroyuki

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