title: [Protective effect of minocycline on glutamate-induced retinal ganglion cell injury and molecular mechanism].
abstract: OBJECTIVE
  To investigate the protective effect and molecular mechanism of minocycline on toxicity of retinal ganglion cells induced by L-glutamate.
  
  
  METHODS
  Primary mouse retinal ganglion cells (RGC) were isolated from mouse retinal in vitro. RGC were divided into control group, L-glutamate group, and L-glutamate + minocycline group, the cell survival rate and nerve axon growth length were observed. In vivo study, B6 mice was intravitreal injected with 2 µl L-glutamate (2 mmol/L) to construct a toxic damage to retinal ganglion cells animal model. One day before the beginning of the experiment, mice were daily intraperitoneal injected with minocycline (60 mg/kg, saline injected in the control group) till day 7, β3 tubulin positive cells and retinal GFAP protein expression were evaluated by tissue i mmol/L unofluorescence assay. Real-time PCR and Western blot assay were used to detect IFN-γ, IL-1, TNF-α and GFAP and vimentin mRNA and protein expression level in retinal tissues.
  
  
  RESULTS
  Compared with control group, RGC survival rate in L-glutamate group was significantly reduced with a dose-and time-dependent. In addition, axon growth was inhibited with the treatment of glutamic acid, while these effects were abolished in the minocycline group (F = 18.87, P < 0.01). Animal study showed that the number of RGC dramatically decreased, however, expression of GFAP in retinal tissue significantly increased in L-glutamate treated mice, compared to control (F = 7.6, P < 0.01). Minocycline treatment significantly improved L-glutamate-induced ganglion cell damage and significantly reduced their GFAP expression. Both mRNA and protein expression levels of IFN-γ, IL-1, TNF-α and GFAP and Vimentin in retinal tissue of L-glutamic acid group significantly upregulated compared to control, while the minocycline significantly reduced the expression of these factors.
  
  
  CONCLUSIONS
  L-glutamic acid can induce retinal ganglion cells damage, inhibit axon growth and increase inflammatory and glial-cell related genes and proteins expression. Minocycline could significantly protect retinal ganglion cells from the injury caused by L-glutamate.
authors.affiliation: The Second Xiangya Hospital of Central South University, Changsha 410011, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Luo-sheng
authors.initials: LS
authors.lastname: Tang
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008911:Minocycline / Q000494:pharmacology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects*
chemical_list: D018698:Glutamic Acid; D008911:Minocycline