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M. Pease, D. J. Zack, C. Berlinicke, K. Bloom, F. Cone, Y. Wang, R. L. Klein, W. W. Hauswirth, H. A. Quigley; CNTF Over-Expression Leads to Increased Retinal Ganglion Cell Survival in Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4052.
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To assess the neuroprotective effect of virally-mediated over-expression of ciliary derived neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in experimental rat glaucoma.
Laser-induced glaucoma was produced in one eye of 224 Wistar rats after injection of adneo-associated viral vectors (type 2) containing either CNTF, BDNF, or both, using saline injected eyes and uninjected glaucoma eyes as controls. IOP was measured with the TonoLab and semi-automated 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 BNDF.
By multivariate regression, CNTF had a significant protective effect, with 15% less RGC axon loss (p < 0.01). Both combined CNTF-BNDF and BDNF over-expression 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.
These data confirm that CNTF can exert a protective effect in experimental glaucoma. The reason for a lack of observed effect with the BDNF over-expression groups is unclear, but may be a function of the level of neurotrophin expression achieved.
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