September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
HistoneH2B, a potential role of cell death ligand, induced RGC death through Toll like receptor 4 in the vitreous of acute angle closure.
Author Affiliations & Notes
  • Yasunari Munemasa
    Ophthalmology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Yasushi Kitaoka
    Ophthalmology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Kana Sase
    Ophthalmology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Kaori Kojima
    Ophthalmology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Akira shiono
    Ophthalmology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Jiro Kogo
    Ophthalmology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Naohito Tokuda
    Ophthalmology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Hitoshi Takagi
    Ophthalmology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Footnotes
    Commercial Relationships   Yasunari Munemasa, None; Yasushi Kitaoka, None; Kana Sase, None; Kaori Kojima, None; Akira shiono, None; Jiro Kogo, None; Naohito Tokuda, None; Hitoshi Takagi, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2529. doi:
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      Yasunari Munemasa, Yasushi Kitaoka, Kana Sase, Kaori Kojima, Akira shiono, Jiro Kogo, Naohito Tokuda, Hitoshi Takagi; HistoneH2B, a potential role of cell death ligand, induced RGC death through Toll like receptor 4 in the vitreous of acute angle closure.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2529.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To investigate the level of histoneH2B (H2B) in the vitreous of acute angle closure (APAC), and its role in the retina. To investigate the level of histone H2B (H2B) in the vitreous of acute angle closure (APAC), and its role in the retina.

Methods : Seven cases of AAC were treated with transconjunctival single-port 25-gauge pars planner vitrectomy followed by lensectomy and IOL implantation. The concentration of H2B was measured by enzyme-linked immunosorbent assay. Retinal damage was evaluated by OCT.
The mass spectrometry (MALDI-TOF MS) was used to detect the ligand of TLR4 in mice RGC degeneration. Pull down assay was performed to confirm cell-cell interaction using histag H2B and immune blot with histag antibody. Toll like receptor 4 (TLR4) knock out mice (TLR4-/-) was used to confirm the role of H2B as a cell death ligand of TLR4.
Effect of intravitreal injection (IVI) of H2B on RGC was evaluated by whole mount retina with retrograde fluorogold RGC labelling. Change of Inflammatory cytokines, such as IL-1β , TNF α, TGF-β after IVI of H2B were studied by real time PCR. The phosphorylation of MAPKs, including p-ERK, p-P38, and p-JNK was studied by immunoblot analysis.

Results : A significant increase in H2B was observed in patients with AAC (24.6 ± 4.5 ng/ml), compared with those control. The change of GCA thickness (1 month and 12 month post operation) was correlated with H2 concentration (R2=0.033, P=0.033). IVI of 300 µmol H2B on wild mice showed significant RGC loss compared with the control (control 1.0 fold/control, H2B 0.75 fold/control, n=5, p=0.009). IVI of H2B on TLR4-/- mice did not show RGC loss compared to wild mice (TLR4-/- 0.92 fold/control, n=5, wild mice 0.66 fold/control, n = 5, P=0.009).
Dramatic upregulation of inflammatory cytokines mRNA was observed in the retina after IVI of H2B, suppression of these changes was observed in TLR4-/- mice (IL-1β; wild 118.0 TLR4-/- 22.4 fold/control, TNF α; wild 37.7 TLR4-/- 3.4, TGF-β; wild 3.1 TLR4-/- 1.1). Furthermore, significant phosphorylation of JNK and P38 was observed in wild mice, in contrast, no obvious phosphorylation of these proteins was observed in TLR4-/- mice.

Conclusions : H2B, a ligand of TLR4, may be one of death ligand of RGC in APAC through inflammatory reactions and subsequent phosphorylation of MAPKs.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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