title: Axonal protection by brimonidine with modulation of p62 expression in TNF-induced optic nerve degeneration.
abstract: OBJECTIVE
  The p62, also called sequestosome 1 (SQSTM1), plays a crucial role in tumor necrosis factor (TNF)-induced optic nerve degeneration. Brimonidine has been shown to have protective effects on retinal ganglion cell bodies, although its role in their axons remains to be examined. We determined whether brimonidine modulates axonal loss induced by TNF and affects the expression of p62 in the optic nerve.
  
  
  METHODS
  Experiments were performed on adult male Wistar rats that received an intravitreal injection of 10 ng TNF alone or simultaneous injection of TNF and 2, 20, or 200 pmol of brimonidine tartrate. The expression of p62 in the optic nerve was examined by immunoblot analysis. The effects of brimonidine on axons were evaluated by counting axon numbers 2 weeks after intravitreal injection.
  
  
  RESULTS
  Intravitreal injection of brimonidine exerted substantial axonal protection against TNF-induced optic nerve degeneration. Immunoblot analysis showed that p62 was upregulated in the optic nerve after intravitreal injection of TNF, and that this increase was completely inhibited by brimonidine. Treatment with brimonidine alone also significantly decreased p62 protein levels in the optic nerve compared with the basal level.
  
  
  CONCLUSIONS
  These results suggest that the modulation of p62 levels in the optic nerve by brimonidine may be involved partly in its axonal protection.
authors: Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan, kitaoka@marianna-u.ac.jp.
authors: Yasushi
authors: Y
authors: Kitaoka
authors: Kaori
authors: K
authors: Kojima
authors: Yasunari
authors: Y
authors: Munemasa
authors: Kana
authors: K
authors: Sase
authors: Hitoshi
authors: H
authors: Takagi
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000627:therapeutic use*; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D000068438:Brimonidine Tartrate / Q000627:therapeutic use*; D002452:Cell Count; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000378:metabolism*; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D058449:Intravitreal Injections; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009901:Optic Nerve Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D000071456:Sequestosome-1 Protein; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D006360:Heat-Shock Proteins; D000071456:Sequestosome-1 Protein; C491079:Sqstm1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D000068438:Brimonidine Tartrate