April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
CNTF Over-Expression Leads to Increased Retinal Ganglion Cell Survival in Experimental Glaucoma
Author Affiliations & Notes
  • M. Pease
    Ophthalmology,
    Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • D. J. Zack
    Ophthalmology,
    Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • C. Berlinicke
    Ophthalmology,
    Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • K. Bloom
    Ophthalmology,
    Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • F. Cone
    Ophthalmology,
    Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • Y. Wang
    Ophthalmology,
    Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • R. L. Klein
    Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana
  • W. W. Hauswirth
    Molecular Genetics and Microbiology, University of Florida, Gainsville, Florida
  • H. A. Quigley
    Dana Center for Preventative Ophthalmology,
    Johns Hopkins University, Wilmer Eye Institute, Baltimore, Maryland
  • Footnotes
    Commercial Relationships  M. Pease, None; D.J. Zack, None; C. Berlinicke, None; K. Bloom, None; F. Cone, None; Y. Wang, None; R.L. Klein, None; W.W. Hauswirth, AGTC, Inc, C; H.A. Quigley, None.
  • Footnotes
    Support  NIH EY02120, EY01765, EY13729, EY11123, EY08571, Research to Prevent Blindness, and Leonard Wagner Trust
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4052. doi:
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    • Get Citation

      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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: neuroprotection • ganglion cells • optic nerve 
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