title: Minocycline protects retinal ganglion cells after optic nerve crush injury in mice by delaying autophagy and upregulating nuclear factor-κB2.
abstract: BACKGROUND
  Currently, no medicine is available that can prevent or treat neural damage associated with optic nerve injury. Minocycline is recently reported to have a neuroprotective function. The aims of this study were to exarmine the neuroprotective effect of minocycline on retinal ganglion cells (RGCs) and determine its underlying mechanisms, using a mouse model of optic nerve crush (ONC).
  
  
  METHODS
  ONC was performed in the left eye of adult male mice, and the mice were randomly divided into minocycline-treated group and saline-treated control group. The mice without receiving ONC injury were used as positive controls. RGC densities were assessed in retinal whole mounts with immunofluorescence labeling of βIII-tubulin. Transmission electron microscopy was used to detect RGC morphologies, and Western blotting and real-time PCR were applied to investigate the expression of autophagy markers LC3-I, LC3-II, and transcriptional factors nuclear factor-κB1 (NF-κB1), NF-κB2.
  
  
  RESULTS
  In the early stage after ONC (at Days 4 and 7), the density of RGCs in the minocycline-treated group was higher than that of the saline-treated group. Electron micrographs showed that minocycline prevented nuclei and mitochondria injuries at Day 4. Western blotting analysis demonstrated that the conversion of LC3-I to LC3-II was reduced in the minocycline-treated group at Days 4 and 7, which meant autophagy process was inhibited by minocycline. In addition, the gene expression of NF-κB2 was upregulated by minocycline at Day 4.
  
  
  CONCLUSIONS
  The neuroprotective effect of minocycline is generated in the early stage after ONC in mice, partly through delaying autophagy process and regulating NF-κB2 pathway.
authors.affiliation: Department of Ophthalmology, Peking University First Hospital; Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing 100034, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Department of Ophthalmology, Peking University First Hospital; Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing 100034, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Ophthalmology, Peking University First Hospital; Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing 100034, China. Email: lucy02114@163.com.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D008297:Male; D051379:Mice; D008911:Minocycline / Q000627:therapeutic use*; D052003:NF-kappa B p52 Subunit / Q000378:metabolism*; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D052003:NF-kappa B p52 Subunit; D008911:Minocycline