title: Adenovirus-mediated expression of ciliary neurotrophic factor (CNTF) rescues axotomized rat retinal ganglion cells but does not support axonal regeneration in vivo.
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.
authors.affiliation: Department of Neurology, University of Tübingen Medical School, Tübingen, D-72076, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Weise
authors.forename: S
authors.initials: S
authors.lastname: Isenmann
authors.forename: N
authors.initials: N
authors.lastname: Klöcker
authors.forename: S
authors.initials: S
authors.lastname: Kügler
authors.forename: S
authors.initials: S
authors.lastname: Hirsch
authors.forename: C
authors.initials: C
authors.lastname: Gravel
authors.forename: M
authors.initials: M
authors.lastname: Bähr
mesh_terms: 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
chemical_list: D020934:Ciliary Neurotrophic Factor