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 | |
| Publication status | Published - Jan 2 2018 |
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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 journal › Article
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=85050729717&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050729717&partnerID=8YFLogxK
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 -