title: Pyroglutamic acid promotes survival of retinal ganglion cells after optic nerve injury.
abstract: OBJECTIVE
  To determine whether pyroglutamic acid (PGA) enhances the survival of retinal ganglion cells (RGCs) after optic nerve (ON) transection in vivo and RGCs in culture.
  
  
  METHODS
  The RGCs of rats were retrogradely labeled by Fluorogold (FG)-soaked sponges placed on both superior colliculi. Seven days later, the ON was transected, and PGA was immediately injected into the vitreous. Seven or fourteen days later, the number of FG-labeled RGCs was counted on flat-mounted retinas to obtain the mean densities of FG-labeled RGCs. To determine whether the survival effect of PGA was related to excitatory amino acid transporter (EAAT), L-trans-pyrrolidine-2,4 dicarboxylate (PDC), a nonselective glutamate transport inhibitor, was injected into vitreous with the PGA. In primary retinal cultures, RGCs were identified as cells that were immunopositive to beta III tubulin three days after beginning the culture with and without PDC.
  
  
  RESULTS
  The mean density of FG-labeled RGCs was reduced from 2249 +/- 210 to 920 +/- 202 cells/mm(2) (p < 0.001) on day 7 after the ON transection. The mean density RGCs was significantly higher at 1213 +/- 159 cells/mm(2) after 0.5% PGA injection immediately after the ON transaction than eyes injected with the vehicle at 1007 +/- 122 cells/mm(2) (p = 0.035). One percent PGA was the most effective concentration for survival-promoting effects on RGCs, and the mean density of the RGCs was 1464 +/- 102/mm(2) (p < 0.001). Fourteen days after 1% PGA, the mean density of FG-labeled RGCs was significantly higher than that with vehicle (204 +/- 23/mm(2) versus 145 +/- 17 cells/mm(2); p < 0.01). Simultaneous application of 1% PGA and PDC blocked the survival effects of PGA on day 7 after ON transection. The presence of PGA increased the number of beta III tubulin-positive cells.
  
  
  CONCLUSIONS
  PGA promotes the survival of axotomized RGCs in adult mammalian retinas possibly mediated by the EAATs.
authors.affiliation: Department of Ophthalmology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Shinichirou
authors.initials: S
authors.lastname: Oono
authors.forename: Takuji
authors.initials: T
authors.lastname: Kurimoto
authors.forename: Toru
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Norio
authors.initials: N
authors.lastname: Okamoto
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kashimoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tagami
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Ito
authors.forename: Osamu
authors.initials: O
authors.lastname: Mimura
mesh_terms: D000818:Animals; D019771:Axotomy; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003998:Dicarboxylic Acids / Q000494:pharmacology; D050491:Glutamate Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007267:Injections; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009900:Optic Nerve / Q000601:surgery; D011759:Pyrrolidines / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism; D013266:Stilbamidines; D014404:Tubulin / Q000378:metabolism; D014822:Vitreous Body
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D003998:Dicarboxylic Acids; D050491:Glutamate Plasma Membrane Transport Proteins; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D013266:Stilbamidines; C488416:Tubb3 protein, rat; D014404:Tubulin; C083486:pyrrolidine-2,4-dicarboxylic acid; D011761:Pyrrolidonecarboxylic Acid