title: Protective effect of P7C3 on retinal ganglion cells from optic nerve injury.
abstract: OBJECTIVE
  To determine whether P7C3-A20, a proneurogenic neuroprotective agent, can protect the retinal ganglion cells (RGCs) of rats from optic nerve crushing.
  
  
  METHODS
  The left optic nerve of 67 rats was crushed, and 5.0 mg/kg/day of P7C3-A20 (crush-P7C3) or its vehicle (crush-placebo) was injected intraperitoneally for 3 days from one day prior to the crushing. The protective effects were determined by the number of Tuj-1-stained RGCs and by the ratio of the mRNA levels of BAX/Bcl-2 on day 7. The levels of NAD and NAD-related genes were also determined.
  
  
  RESULTS
  The density of RGCs was 2009.4 ± 57.7 cells/mm2in the sham controls; it was significantly lower in the crush-placebo group at 979.7 ± 144.3 cells/mm2(P < 0.0001). The neuroprotective effects of P7C3-A20 was demonstrated by the significantly higher density of 1266.0 ± 193.1 cells/mm2than in the crush-placebo group (P = 0.01, Scheffe). After crushing the optic nerve the BAX/Bcl-2 ratio was higher in the optic nerves and retina, application of P7C3-A20 significantly reduced this ratio. P7C3-A20 significantly increased the NAD level in the untouched optic nerves from 1.36 ± 0.05 to 1.59 ± 0.10 nmol/mg protein (P = 0.02, t test). Crushing the optic nerve decreased the level to 1.27 ± 0.21 nmol/mg protein and P7C3-A20 preserved the level at 1.43 ± 0.10 nmol/mg protein. Crushing the optic nerve decreased the mRNA levels of Nampt and Sirt-1 in the optic nerves, while P7C3-A20 significantly restored the levels.
  
  
  CONCLUSIONS
  P7C3-A20 can protect RGCs from optic nerve crushing possibly through preserving the NAD levels in the optic nerves.
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan. hidehirooku@aol.com.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Oku
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Seita
authors.initials: S
authors.lastname: Morishita
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Horie
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishikawa
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Teruyo
authors.initials: T
authors.lastname: Kida
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mimura
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Kojima
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D020221:Optic Nerve Injuries / Q000175:diagnosis / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology
chemical_list: D002227:Carbazoles; C552520:P7C3 compound
keywords: NAD; NAMPT; Optic nerve crush; P7C3; SIRT-1