Effect of CNTF on retinal ganglion cell survival in experimental glaucoma.
OBJECTIVE
To assess the neuroprotective effect of virally mediated overexpression of ciliary-derived neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in experimental rat glaucoma.


METHODS
Laser-induced glaucoma was produced in one eye of 224 Wistar rats after injection of adenoassociated viral vectors (type 2) containing either CNTF, BDNF, or both, with saline-injected eyes and noninjected glaucomatous eyes serving as the control. IOP was measured with a hand-held tonometer, and semiautomated optic nerve axon counts were performed by masked observers. IOP exposure over time was adjusted in multivariate regression analysis to calculate the effect of CNTF and BDNF.


RESULTS
By multivariate regression, CNTF had a significant protective effect, with 15% less RGC axon death (P < 0.01). Both combined CNTF-BDNF and BDNF overexpression alone had no statistically significant improvement in RGC axon survival. By Western blot, there was a quantitative increase in CNTF and BDNF expression in retinas exposed to single viral vectors carrying each gene, but no increase with sequential injection of both vectors.


CONCLUSIONS
These data confirm that CNTF can exert a protective effect in experimental glaucoma. The reason for the lack of observed effect in the BDNF overexpression groups is unclear, but it may be a function of the level of neurotrophin expression achieved.
Pease
Mary Ellen
ME
Department of Ophthalmology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, 175 Woods Research Building, Baltimore, MD 21287, USA. mpease@jhmi.edu
Zack
Donald J
DJ
Berlinicke
Cynthia
C
Bloom
Kristen
K
Cone
Frances
F
Wang
Yuxia
Y
Klein
Ronald L
RL
Hauswirth
William W
WW
Quigley
Harry A
HA
D000818:Animals; D001369:Axons / Q000473:pathology; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D020934:Ciliary Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D019610:Cytoprotection / Q000235:genetics*; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D015316:Genetic Therapy; D005822:Genetic Vectors; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007429:Intraocular Pressure; D008297:Male; D009901:Optic Nerve Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D014065:Tonometry, Ocular
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor