May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Modulation of Retinal Glial Activation Using Cell-Cycle Inhibitors
Author Affiliations & Notes
  • F. R. Vazquez-Chona
    Ophthalmology, Univ of Utah, Salt Lake, Utah
  • R. E. Marc
    Ophthalmology, Univ of Utah, Salt Lake, Utah
  • E. M. Levine
    Ophthalmology, Univ of Utah, Salt Lake, Utah
  • Footnotes
    Commercial Relationships F.R. Vazquez-Chona, None; R.E. Marc, None; E.M. Levine, None.
  • Footnotes
    Support REM: R01 EY002576 HIGHWIRE EXLINK_ID="48:5:2505:1" VALUE="EY002576" TYPEGUESS="GEN" /HIGHWIRE , R01 EY015128 HIGHWIRE EXLINK_ID="48:5:2505:2" VALUE="EY015128" TYPEGUESS="GEN" /HIGHWIRE , P30 EY014800 HIGHWIRE EXLINK_ID="48:5:2505:3" VALUE="EY014800" TYPEGUESS="GEN" /HIGHWIRE ; EML R01 EY0137; Unrestricted funding from Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2505. doi:
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      F. R. Vazquez-Chona, R. E. Marc, E. M. Levine; Modulation of Retinal Glial Activation Using Cell-Cycle Inhibitors. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2505.

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

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Purpose:: Virtually all retinal degenerations activate a complex series of events in glial cells that compromises the function of the retina. Retinal glia cells include Muller glia, astrocytes, and microglia. Chronic or acute activation of glia results in abnormal hypertrophy, proliferation, migration, and inflammation. We are testing the hypothesis that the response of retinal glia to trauma and degeneration is controlled by intrinsic cell-cycle dysregulation.

Methods:: To test our hypothesis we are using microarray, genetic, and pharmacological approaches. Microarray experiments are surveying the cell-cycle genes that change after trauma to the retina (mechanical tear and ON crush). Genetic experiments involve examining the effect of inactivating the cell-cycle inhibitor p27Kip on glial differentiation and glial response to trauma. Pharmacological experiments are screening a library of small-molecule cell-cycle inhibitors using an organotypic model of retinal degeneration. Quantification analyses for the screen include immunohistochemistry and computational molecular phenotyping.

Results:: Microarray analyses of retinal injury models show that the earlier stages of degeneration are characterized by dysregulation of cell-cycle gene expression [Vazquez et al., 2004]. Genetic studies show that mice with the deletion of the cell-cycle inhibitor p27Kip display Muller glial dysplasia and GFAP expression [Levine et al., 2001].

Conclusions:: Our genetic and gene-expression studies suggest that aberrant cell-cycle entry modulates retinal glial reactivity. Studies by others confirmed that reactive Muller glia express changes in cell-cycle regulators (cyclin D3, cyclin B1, p53, and p27Kip1). Moreover in traumatic brain injury, small molecules that inhibit the cell cycle decreased glial scar formation and provided neuroprotection [Di Giovanni et al., 2005]. Thus, our long term goal is to identify pharmacological cell-cycle inhibitors that prevent glial damage and provide neuroprotection.

Keywords: retinal degenerations: cell biology • neuroprotection • retinal glia 

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