title: Amino-Nogo inhibits optic nerve regeneration and functional recovery via the integrin αv signaling pathway in rats.
abstract: BACKGROUND
  Nogo-A, a major myelin-associated inhibitor, can inhibit injured optic nerve regeneration. However, whether Amino-Nogo is the most important functional domain of Nogo-A remains unknown. This study aimed to identify the role of Amino-Nogo following optic nerve injury, and the mechanism of the Amino-Nogo-integrin αv signaling pathway in vivo.
  
  
  METHODS
  Sprague-Dawley rats with optic nerve crush injury were injected with Nogo-A siRNA (Nogo-A-siRNA), the Nogo-66 functional domain antagonist peptide of Nogo-A (Nep1-40) or a recombinant rat Amino-Nogo-A protein (∆20) into the vitreous cavity to knock down Nogo-A, inhibit Nogo-66 or activate the Amino-Nogo, resparately. Retinal ganglion cell (RGC) density, axon regeneration and the pattern of NPN of visual electrophysiology (flash visual evoked potentials [F-VEP]) at different times post-injury were investigated.
  
  
  RESULTS
  Our study revealed a lower RGC survival rate; shorter axonal outgrowth; longer N1, P1 and N2 waves latencies; and lower N1-P1 and P1-N2 amplitudes in the Δ20 group, and Δ20 treatment significantly attenuated integrin αv expression and phosphorylated focal adhesion kinase (p-FAK) levels. In the Nep1-40 and Nogo-A siRNA groups, there were higher RGC survival rates, longer axonal outgrowth, shorter N1 and P1 wave latencies, and higher N1-P1 and P1-N2amplitudes. Nogo-A siRNA treatment significantly increased integrin αv expression and p-FAK levels. Nepl-40 treatment did not alter integrin αv expression. In addition, there was no significant change in integrin α5 in any group.
  
  
  CONCLUSIONS
  These results suggest that the integrin signaling pathway is regulated by Amino-Nogo, which inhibits optic nerve regeneration and functional recovery, and that the integrin subunit involved might be integrin αv but not integrin α5.
authors.affiliation: Department of Ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huo
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Yin
authors.forename: Shu-Xing
authors.initials: SX
authors.lastname: Ji
authors.forename: Huan
authors.initials: H
authors.lastname: Zou
authors.forename: Min
authors.initials: M
authors.lastname: Lang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zheng
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Chen
authors.forename: Yuan-Guo
authors.initials: YG
authors.lastname: Zhou
authors.forename: Rong-Di
authors.initials: RD
authors.lastname: Yuan
authors.forename: Jian
authors.initials: J
authors.lastname: Ye
mesh_terms: D000818:Animals; D005074:Evoked Potentials, Visual; D055785:Gene Knockdown Techniques; D039564:Integrin alphaV / Q000378:metabolism*; D009185:Myelin Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D009416:Nerve Regeneration; D000070798:Nogo Proteins; D009900:Optic Nerve / Q000166:cytology / Q000503:physiopathology*; D020221:Optic Nerve Injuries / Q000378:metabolism / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D039564:Integrin alphaV; D009185:Myelin Proteins; C457761:NEPI-40 protein, rat; D000070798:Nogo Proteins; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C000603197:Rtn4 protein, rat