May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Exogenous Modulation of Intrinsic Optic Nerve Neuroprotective Activity in Rodent Eyes Exposed to Elevated Intraocular Pressure
Author Affiliations & Notes
  • S. D. Grozdanic
    Iowa State University, Ames, Iowa
    Veterinary Clinical Sciences,
  • D. S. Sakaguchi
    Iowa State University, Ames, Iowa
    Genetics, Development and Cell Biology,
  • M. S. Kuehn
    Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa
  • E. B. Lavik
    Biomedical Engineering, Yale University, New Haven, Connecticut
  • Y. H. Kwon
    Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa
  • R. H. Kardon
    Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa
  • Footnotes
    Commercial Relationships S.D. Grozdanic, None; D.S. Sakaguchi, None; M.S. Kuehn, None; E.B. Lavik, None; Y.H. Kwon, None; R.H. Kardon, None.
  • Footnotes
    Support Veterans Health Administration, Rehabilitation Research and Development Service Grant C3919R, The Glaucoma Foundation, NY; NINDS Grant NS 44007; Research to Prevent Blindness, NY
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 4378. doi:
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    • Get Citation

      S. D. Grozdanic, D. S. Sakaguchi, M. S. Kuehn, E. B. Lavik, Y. H. Kwon, R. H. Kardon; Exogenous Modulation of Intrinsic Optic Nerve Neuroprotective Activity in Rodent Eyes Exposed to Elevated Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4378.

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

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Abstract

Purpose:: To characterize functional status of the rat retina and optic nerve after acute elevation of intraocular pressure (IOP) and determine molecular signature of the observed spontaneous recovery of optic nerve function.

Methods:: Retinal ischemia was induced in rats by increasing the IOP (110 mmHg/60 minutes). Microarray analysis, RT-PCR and immunohistochemistry were used to characterize retinal tissue. PLGA microspheres for sustained delivery over 60 days of neurotrophic factors (BDNF, GDNF, CNTF or blank/control) were injected into the vitreous 1 day after elevation of IOP. The pupil light reflex parameters (PLR) and electroretinograms (flash and flicker ERG, oscillatory potentials) were monitored for 60 days postoperatively.

Results:: Detailed analysis of PLR amplitudes showed significant, but temporary recovery in function at 28 days postop in rats which were not treated or received empty microspheres. Molecular analysis showed significant up-regulation of CNTF (p<0.05), with strong correlation between CNTF expression and PLR recovery (r2=0.79, p=0.01). Molecular profiling showed decreased expression of the GDNF receptor in the first 10 days after IOP elevation, however expression was normal at 28 days postoperatively. Analysis of BDNF and its receptors did not show change in expression. Animals that received CNTF microspheres did not have significant functional recovery compared to animals which received empty microspheres (p>0.05). Animals that received GDNF microspheres did not show any functional recovery in the first 10 days after treatment (p>0.1), however PLR function significantly improved at later time points corresponding to the recovery of GDNF receptor expression. Animals that received BDNF microspheres had immediate functional recovery, which was sustained until the end of experiment. ERG data analysis revealed no statistically significant difference between all groups.

Conclusions:: The results suggest neurotrophic growth factors may protect optic nerve function against ocular hypertension but only: 1) if exogenously applied neurotrophic factors are not already intrinsically produced at maximal therapeutic concentrations in the affected tissue; 2) if receptors for the exogenously applied neurotrophic factors are still present in sufficient amount in the affected tissue to mediate effective biological activity.

Keywords: neuroprotection • growth factors/growth factor receptors • ganglion cells 
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