Increased expression of M-CSF and IL-13 in vitreous of patients with proliferative diabetic retinopathy: Implications for M2 macrophage-involving fibrovascular membrane formation

Shigeo Yoshida, Yoshiyuki Kobayashi, Takahito Nakama, Yedi Zhou, Keijiro Ishikawa, Ryoichi Arita, Shintaro Nakao, Masanori Miyazaki, Yukio Sassa, Yuji Oshima, Kenji Izuhara, Toshihiro Kono, Tatsuro Ishibashi

Research output: Contribution to journalArticle

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Abstract

Purpose: We recently demonstrated that M2 macrophages were involved in the development of fibrovascular membranes (FVM) associated with proliferative diabetic retinopathy (PDR) possibly through the induction of periostin. The purpose of this study was to determine whether macrophage colony-stimulating factor (M-CSF) and interleukin (IL)-13, inducers of the M2 polarisation of macrophages from monocytes, are elevated in the vitreous of patients with PDR, and whether M2-polarised macrophages induce periostin production. Methods: We measured the levels of M-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, IL-13, soluble (s)CD163, periostin and vascular endothelial growth factor by sandwich ELISA in vitreous samples collected from 61 eyes of 47 patients with PDR, and 39 eyes of 36 patients with non-diabetic ocular diseases (control group). Human monocytes were polarised in vitro with GM-CSF, interferon-γ, and lipopolysaccharide for M1 macrophages, and M-CSF, IL-4, and IL-13 for M2 macrophages. Quantitative real-time PCR was used to determine the mRNA level of periostin. Results: The concentrations of M-CSF and IL-13 in the vitreous were significantly higher in patients with PDR than in non-diabetic controls (p<0.0001). There was a strong positive correlation between the vitreous concentrations of M-CSF and sCD163 and periostin. The mean vitreous level of IL-13 was significantly higher in eyes with FVMs than in those without FVMs (epicentre only). In vitro studies showed that M2-polarlised macrophages significantly increased the expression of the mRNA of periostin. Conclusions: These findings indicate that the M2 polarisation of macrophages is induced by M-CSF and IL-13 in diabetic retinas. The presence of M-CSF and IL-13 would then promote FVM formation by periostin production.

Original languageEnglish
Pages (from-to)629-634
Number of pages6
JournalBritish Journal of Ophthalmology
Volume99
Issue number5
DOIs
Publication statusPublished - May 1 2015

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Macrophage Colony-Stimulating Factor
Interleukin-13
Diabetic Retinopathy
Macrophages
Membranes
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-4
Monocytes
Messenger RNA
Eye Diseases
Interferons
Vascular Endothelial Growth Factor A
Lipopolysaccharides
Retina
Real-Time Polymerase Chain Reaction
Enzyme-Linked Immunosorbent Assay
Control Groups

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Increased expression of M-CSF and IL-13 in vitreous of patients with proliferative diabetic retinopathy : Implications for M2 macrophage-involving fibrovascular membrane formation. / Yoshida, Shigeo; Kobayashi, Yoshiyuki; Nakama, Takahito; Zhou, Yedi; Ishikawa, Keijiro; Arita, Ryoichi; Nakao, Shintaro; Miyazaki, Masanori; Sassa, Yukio; Oshima, Yuji; Izuhara, Kenji; Kono, Toshihiro; Ishibashi, Tatsuro.

In: British Journal of Ophthalmology, Vol. 99, No. 5, 01.05.2015, p. 629-634.

Research output: Contribution to journalArticle

Yoshida, Shigeo ; Kobayashi, Yoshiyuki ; Nakama, Takahito ; Zhou, Yedi ; Ishikawa, Keijiro ; Arita, Ryoichi ; Nakao, Shintaro ; Miyazaki, Masanori ; Sassa, Yukio ; Oshima, Yuji ; Izuhara, Kenji ; Kono, Toshihiro ; Ishibashi, Tatsuro. / Increased expression of M-CSF and IL-13 in vitreous of patients with proliferative diabetic retinopathy : Implications for M2 macrophage-involving fibrovascular membrane formation. In: British Journal of Ophthalmology. 2015 ; Vol. 99, No. 5. pp. 629-634.
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abstract = "Purpose: We recently demonstrated that M2 macrophages were involved in the development of fibrovascular membranes (FVM) associated with proliferative diabetic retinopathy (PDR) possibly through the induction of periostin. The purpose of this study was to determine whether macrophage colony-stimulating factor (M-CSF) and interleukin (IL)-13, inducers of the M2 polarisation of macrophages from monocytes, are elevated in the vitreous of patients with PDR, and whether M2-polarised macrophages induce periostin production. Methods: We measured the levels of M-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, IL-13, soluble (s)CD163, periostin and vascular endothelial growth factor by sandwich ELISA in vitreous samples collected from 61 eyes of 47 patients with PDR, and 39 eyes of 36 patients with non-diabetic ocular diseases (control group). Human monocytes were polarised in vitro with GM-CSF, interferon-γ, and lipopolysaccharide for M1 macrophages, and M-CSF, IL-4, and IL-13 for M2 macrophages. Quantitative real-time PCR was used to determine the mRNA level of periostin. Results: The concentrations of M-CSF and IL-13 in the vitreous were significantly higher in patients with PDR than in non-diabetic controls (p<0.0001). There was a strong positive correlation between the vitreous concentrations of M-CSF and sCD163 and periostin. The mean vitreous level of IL-13 was significantly higher in eyes with FVMs than in those without FVMs (epicentre only). In vitro studies showed that M2-polarlised macrophages significantly increased the expression of the mRNA of periostin. Conclusions: These findings indicate that the M2 polarisation of macrophages is induced by M-CSF and IL-13 in diabetic retinas. The presence of M-CSF and IL-13 would then promote FVM formation by periostin production.",
author = "Shigeo Yoshida and Yoshiyuki Kobayashi and Takahito Nakama and Yedi Zhou and Keijiro Ishikawa and Ryoichi Arita and Shintaro Nakao and Masanori Miyazaki and Yukio Sassa and Yuji Oshima and Kenji Izuhara and Toshihiro Kono and Tatsuro Ishibashi",
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T2 - Implications for M2 macrophage-involving fibrovascular membrane formation

AU - Yoshida, Shigeo

AU - Kobayashi, Yoshiyuki

AU - Nakama, Takahito

AU - Zhou, Yedi

AU - Ishikawa, Keijiro

AU - Arita, Ryoichi

AU - Nakao, Shintaro

AU - Miyazaki, Masanori

AU - Sassa, Yukio

AU - Oshima, Yuji

AU - Izuhara, Kenji

AU - Kono, Toshihiro

AU - Ishibashi, Tatsuro

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Purpose: We recently demonstrated that M2 macrophages were involved in the development of fibrovascular membranes (FVM) associated with proliferative diabetic retinopathy (PDR) possibly through the induction of periostin. The purpose of this study was to determine whether macrophage colony-stimulating factor (M-CSF) and interleukin (IL)-13, inducers of the M2 polarisation of macrophages from monocytes, are elevated in the vitreous of patients with PDR, and whether M2-polarised macrophages induce periostin production. Methods: We measured the levels of M-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, IL-13, soluble (s)CD163, periostin and vascular endothelial growth factor by sandwich ELISA in vitreous samples collected from 61 eyes of 47 patients with PDR, and 39 eyes of 36 patients with non-diabetic ocular diseases (control group). Human monocytes were polarised in vitro with GM-CSF, interferon-γ, and lipopolysaccharide for M1 macrophages, and M-CSF, IL-4, and IL-13 for M2 macrophages. Quantitative real-time PCR was used to determine the mRNA level of periostin. Results: The concentrations of M-CSF and IL-13 in the vitreous were significantly higher in patients with PDR than in non-diabetic controls (p<0.0001). There was a strong positive correlation between the vitreous concentrations of M-CSF and sCD163 and periostin. The mean vitreous level of IL-13 was significantly higher in eyes with FVMs than in those without FVMs (epicentre only). In vitro studies showed that M2-polarlised macrophages significantly increased the expression of the mRNA of periostin. Conclusions: These findings indicate that the M2 polarisation of macrophages is induced by M-CSF and IL-13 in diabetic retinas. The presence of M-CSF and IL-13 would then promote FVM formation by periostin production.

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