Adenovirus-mediated expression of ciliary neurotrophic factor (CNTF) rescues axotomized rat retinal ganglion cells but does not support axonal regeneration in vivo.
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.
Weise
J
J
Department of Neurology, University of Tübingen Medical School, Tübingen, D-72076, Germany.
Isenmann
S
S
Klöcker
N
N
Kügler
S
S
Hirsch
S
S
Gravel
C
C
Bähr
M
M
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001369:Axons / Q000502:physiology; D019771:Axotomy; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage / Q000235:genetics* / Q000502:physiology*; D003714:Denervation; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology; D009900:Optic Nerve / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D014822:Vitreous Body / Q000502:physiology
D020934:Ciliary Neurotrophic Factor