title: Neuropeptide FF Promotes Recovery of Corneal Nerve Injury Associated With Hyperglycemia.
abstract: OBJECTIVE
  To investigate how the neuropeptide FF (NPFF) promotes the recovery of corneal nerve injury associated with hyperglycemia.
  
  
  METHODS
  Gene expression was analyzed using neurotrophin and receptor RT2 profiler polymerase chain reaction arrays in trigeminal (TG) sensory neurons. The role of NPFF in the regeneration of diabetic TG nerves was investigated in vitro by using cultured TG neurons from diabetic BKS.Cg-m+/+Leprdb/J (db/db) mice and in vivo by following corneal injury healing responses. RF9, a selective NPFF receptor (NPFF2R) antagonist, was used to prevent the interactions between NPFF and NPFF2R.
  
  
  RESULTS
  Using a mRNA real-time PCR array, NPFF was found to be significantly lower in diabetic TG sensory neurons. Hyperglycemia induced the deficiency of ocular properties in db/db mice. The application of NPFF enhanced neurite elongation in diabetic TG neurons. Through subconjunctival injection, NPFF promoted corneal nerve injury recovery and epithelial wound healing in db/db mice. Furthermore, the application of NPFF rescued the activation of SIRT1 and PPAR-gamma, and downregulated the expression of PTEN and Rb in diabetic TG neurons. The promotion of NPFF on diabetic corneal epithelial healing and corneal innervations was completely abolished by RF9. Moreover, subconjunctivally injected NPFF accelerated the reinnervation of corneal nerves via the ERK1/2 pathway.
  
  
  CONCLUSIONS
  These results indicate that NPFF signaling through NPFFR2 contributes to diabetic corneal nerve injury recovery and epithelial wound healing. Neuropeptide FF is a potential neuroregenerative factor for diabetic sensory nerve injury. Chinese Abstract.
authors.forename: Yunhai
authors.initials: Y
authors.lastname: Dai
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zhao
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Lixin
authors.initials: L
authors.lastname: Xie
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003315:Cornea / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D020127:Recovery of Function; D015398:Signal Transduction; D012668:Trigeminal Ganglion / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor