Combined effect of olfactory ensheathing cell (OEC) transplantation and glial cell line-derived neurotrophic factor (GDNF) intravitreal injection on optic nerve injury in rats

Mol Vis. 2010 Dec 28:16:2903-10.

Abstract

Purpose: To investigate the combined effect of olfactory ensheathing cell (OEC) transplantation and recombinant human glial cell line-derived neurotrophic factor (rhGDNF) intravitreal injection on optic nerve functional recovery following incomplete injury in adult rats.

Methods: The optic nerves of adult rats were crushed by forceps and then GDNF was injected into vitreous cavity, OECs transplanted into injured optic nerve, or GDNF vitreous injection combined with OECs transplantation, and balanced salt solution was injected into vitreous cavity of control group rats respectively. Flash visual evoked potential (F-VEP) was performed on the injured eye immediately after injury and at 1, 2, 4, and 8 weeks after injury.

Results: The F-VEP waveforms were almost silent immediately after the optic nerve injury. The latency of the F-VEP (LP1) recovered nearly to the normal value 1 week after injury in the treatment groups. The amplitude recovered more slowly. It recovered more obviously and rapidly in the rhGDNF combined with OEC group. At 8 weeks after injury, the amplitude was restored to 64.5% of the pre-injury level in the control group and to 91.8% in the GDNF+OEC treatment group. Wheat germ agglutinin (WGA) labeling showed retinal ganglion cell (RGC) axon regeneration and prolongation in the combined group, and the regenerated axons extended across the traumatized area and reached the distal end of the injured optic nerve.

Conclusions: The combination of OEC transplantation and rhGDNF intravitreal injection will be more effective in promoting the recovery of visual function after incomplete injury of the optic nerve in adult rats.

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / pathology
  • Cells, Cultured
  • Evoked Potentials, Visual / drug effects
  • Fluorescent Antibody Technique
  • Glial Cell Line-Derived Neurotrophic Factor / administration & dosage*
  • Glial Cell Line-Derived Neurotrophic Factor / pharmacology
  • Glial Cell Line-Derived Neurotrophic Factor / therapeutic use*
  • Humans
  • Intravitreal Injections
  • Male
  • Olfactory Mucosa / cytology*
  • Olfactory Mucosa / drug effects
  • Olfactory Mucosa / transplantation*
  • Optic Nerve Injuries / drug therapy*
  • Optic Nerve Injuries / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Regeneration / drug effects
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / pathology
  • Wheat Germ Agglutinins / metabolism

Substances

  • Glial Cell Line-Derived Neurotrophic Factor
  • Wheat Germ Agglutinins