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Yasunari Munemasa, Kazuhide Takada, Kaori Kojima, Satoki Ueno, Yasushi Kitaoka; The novelty of Toll like receptor-4 ligand and RGC degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2466.
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Toll like receptor-4 (TLR-4) has been indicated in response to various ligands related with cell death signaling, in addition to autoimmune response. The purpose of this study is to investigate the novelty of TLR-4 in RGC degeneration.
Eight week male C3H/HeJ and C3H/HeN mice were used in this study. C3H/HeJ mice show dysfunction of TLR-4. In contrast, C3H/HeN mice show normal TLR-4 function. To generate optic nerve crush (ONC), the nerve of one eye was exposed and clamped approximately 0.5 mm from the globe with self-closing forceps for 10s, contralateral eye was used as a control. RGC was labeled with fluoro-gold at superior colliculus 5 days before ONC and morphological analysis was performed with whole mount retina at 2 weeks after ONC. Matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOFMS) was used to detect TLR-4 ligands after immunoprecipitation with TLR-4 antibody and isolation of retinal membrane proteins at 5 days after ONC. Induction of RGC degeneration with TLR-4 ligand was studied with cell viability assay using RGC-5 cells and intravitreal injection of TLR-4 ligand on C3H/HeJ and C3H/HeN mice.
A significant decrease in RGC was observed in the retina of C3H/HeJ mice compared to C3H/HeN mice 2 weeks after ONC (C3H/HeJ 0.24 fold / control vs C3H/HeN 0.40 fold / control, P < 0.05). MALDI-TOF MS identified Histone H2B type1-B (score129) as the ligand of TLR-4. Histone H2B induced RGC-5 cells death, 0.5 fold / control (P < 0.05). A decrease in RGC density was more apparent in the retina of C3H/HeN mice compared to C3H/HeJ mice at 7 days after intravitreal injection of Histone H2B.
Histone H2B was identified as a novelty of TLR-4 and induced RGC degeneration through TLR-4.
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