March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Temporal Changes In Retinal Gene Expression After Optic Nerve Crush In Mice
Author Affiliations & Notes
  • Tasneem M. Putliwala
    CBAN - Visual Sciences, University of North Texas Health Science Center, North Texas Eye Research Institute, Fort Worth, Texas
  • Colleen McDowell
    CBAN - Visual Sciences, University of North Texas Health Science Center, North Texas Eye Research Institute, Fort Worth, Texas
  • Yang Liu
    CBAN - Visual Sciences, University of North Texas Health Science Center, North Texas Eye Research Institute, Fort Worth, Texas
  • Thomas L. Casavant
    Bioinformatics and Computational Biology, University of IOWA, Iowa City, Iowa
  • Benjamin Faga
    Bioinformatics and Computational Biology, University of IOWA, Iowa City, Iowa
  • David M. Thole
    Bioinformatics and Computational Biology, University of IOWA, Iowa City, Iowa
  • Robert J. Wordinger
    CBAN - Visual Sciences, University of North Texas Health Science Center, North Texas Eye Research Institute, Fort Worth, Texas
  • Terry A. Braun
    Bioinformatics and Computational Biology, University of IOWA, Iowa City, Iowa
  • Abbot F. Clark
    CBAN - Visual Sciences, University of North Texas Health Science Center, North Texas Eye Research Institute, Fort Worth, Texas
  • Footnotes
    Commercial Relationships  Tasneem M. Putliwala, None; Colleen McDowell, None; Yang Liu, None; Thomas L. Casavant, None; Benjamin Faga, None; David M. Thole, None; Robert J. Wordinger, None; Terry A. Braun, None; Abbot F. Clark, None
  • Footnotes
    Support  DoD grant ( W81XWH-10-2-0003 )
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 3847. doi:
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      Tasneem M. Putliwala, Colleen McDowell, Yang Liu, Thomas L. Casavant, Benjamin Faga, David M. Thole, Robert J. Wordinger, Terry A. Braun, Abbot F. Clark; Temporal Changes In Retinal Gene Expression After Optic Nerve Crush In Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3847.

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

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Abstract

Purpose: : Glaucoma is a progressive optic neuropathy characterized by axonal impairment, retinal ganglion cell (RGC) loss, and visual field defects. Understanding temporal global gene expression patterns that eventually lead to RGC death will identify pathways associated with glaucoma pathogenesis. The purpose of this study is to evaluate changes in retinal gene expression using an in vivo optic nerve crush (ONC) mouse model that mimics many features of glaucoma.

Methods: : Unilateral ONC was performed on 8-10-week-old BALB/cJ eyes using the Nickell’s technique. Retinas (N=5) were harvested at six different time points (0, 3, 7, 14, 21, and 28 days) post crush. Pooled RNA samples (N=5/ time point) were run on Affymetrix Mouse Gene array chips. PARTEK ®, STRING and DAVID databases were used for bioinformatic analysis. Temporal expression clusters and network maps were statistically identified (p < 0.05).

Results: : After ONC, gene expression was significantly and temporally altered (p<0.05, fold change of 1.5) in 29 up-regulated clusters and 20 down-regulated clusters, based on the three gene ontologies. Early up-regulated clusters at 3 and 7 days included structural eye proteins, calcium ion binding and extracellular matrix, while later time points showed protein kinase and G-protein coupled receptor activity, ribosome function and sensory perception. No significant changes at early time points in the down-regulated clusters were found; however, by 21 days there was decreased expression in the categories of axonogenesis, neuronal differentiation, microtubule based process, and pattern binding. Key genes in both datasets included GAP43, neuritin 1, synuclein ϒ, neurofilaments, visinilin-like 1, synaptotagmin like 3 and GFAP.

Conclusions: : Temporal changes seen in key genes that down regulate neuronal projection and axonogenesis and up regulate signal transduction and kinase activities will establish novel neuropathy mechanisms. Our findings will be a crucial source of information in the development of therapeutic strategies to prevent the loss of RGCs in optic nerve axonopathy.

Keywords: retina • gene microarray • degenerations/dystrophies 
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