Adenovirus-mediated expression of ciliary neurotrophic factor (CNTF) rescues axotomized rat retinal ganglion cells but does not support axonal regeneration in vivo

Neurobiol Dis. 2000 Jun;7(3):212-23. doi: 10.1006/nbdi.2000.0285.

Abstract

Rat optic nerve (ON) transection leads to mainly apoptotic cell death of about 85% of the retinal ganglion cell (RGC) population within 14 days after lesion. In the present study, we tested the effect of adenovirally delivered CNTF (Ad-CNTF) on survival and regeneration of axotomized adult RGCs in vivo. Single intravitreal Ad-CNTF injection led to stable CNTF mRNA and protein expression for at least 18 days and significantly enhanced RGC survival by 155% when compared to control animals 14 days after ON transection. ON stump application of Ad-CNTF also resulted in an increased number of surviving RGCs. Ad-CNTF injection led to better preservation of intraretinal RGC axons but did not support regeneration of axotomized RGCs into a peripheral nerve graft. Thus, adenovirus-mediated neurotrophic factor supply is a suitable approach for reducing axotomy-induced RGC death in vivo and may constitute a relevant strategy for clinical treatment of traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Axons / physiology
  • Axotomy*
  • Cell Count
  • Cell Death / physiology
  • Ciliary Neurotrophic Factor / administration & dosage
  • Ciliary Neurotrophic Factor / genetics*
  • Ciliary Neurotrophic Factor / physiology*
  • Denervation
  • Female
  • Gene Expression / physiology*
  • Nerve Regeneration / physiology
  • Optic Nerve / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Retina / physiology
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / physiology*
  • Vitreous Body / physiology

Substances

  • Ciliary Neurotrophic Factor