Dose-dependent rescue of axotomized rat retinal ganglion cells by adenovirus-mediated expression of glial cell-line derived neurotrophic factor in vivo.
Adult rat retinal ganglion cells undergo degeneration after optic nerve transection. Repeated intraocular injection of glial cell-line derived neurotrophic factor (GDNF) has been shown to be efficient in enhancing retinal ganglion cell survival following optic nerve axotomy. In the present study we evaluated the potential survival-promoting effect of adenovirally administered GDNF on axotomized retinal ganglion cells. A single intravitreal injection [7 x 107 plaque-forming units (pfu) or 7 x 108 pfu] of an adenoviral vector expressing the rat GDNF gene from a cytomegalovirus promoter enhanced retinal ganglion cell survival 14 days after axotomy by 67 and 125%, respectively, when compared to control animals. Intraocular administration of the vector rescued 12.6 and 23%, respectively, of the retinal ganglion cells which would otherwise have died after axotomy. An increase in retinal GDNF protein and specific virally transduced GDNF mRNA expression was detected following intraocular vector application. Our data support previous findings showing that adenoviral delivery of neurotrophic factors to the vitreous body is a feasible approach for the prevention of axotomy-induced retinal ganglion cell death in vivo and may constitute a relevant strategy for future treatment in traumatic brain injury and ensuing neurodegeneration.
Schmeer
Christian
C
Laboratorio de Neuroquímica, Instituto Venezolano de Investigaciones Científicas, 1020 A Caracas, Venezuela.
Straten
Guido
G
Kügler
Sebastian
S
Gravel
Claude
C
Bähr
Mathias
M
Isenmann
Stefan
S
D000818:Animals; D019771:Axotomy; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005822:Genetic Vectors / Q000494:pharmacology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009414:Nerve Growth Factors; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009900:Optic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D005456:Fluorescent Dyes; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger