April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
NF-kB Regulated Neurotoxicity of Reactive Astrocytes
Author Affiliations & Notes
  • D. J. Barakat
    Graduate Program in Cell Biology & Anatomy,
    University of Miami Miller School of Medicine, Miami, Florida
  • G. Dvoriantchikova
    Department of Ophthalmology,
    University of Miami Miller School of Medicine, Miami, Florida
  • D. Ivanov
    Department of Ophthalmology,
    University of Miami Miller School of Medicine, Miami, Florida
  • R. Brambilla
    Department of Neurological Surgery,
    University of Miami Miller School of Medicine, Miami, Florida
  • V. I. Shestopalov
    Department of Ophthalmology,
    University of Miami Miller School of Medicine, Miami, Florida
  • Footnotes
    Commercial Relationships  D.J. Barakat, None; G. Dvoriantchikova, None; D. Ivanov, None; R. Brambilla, None; V.I. Shestopalov, None.
  • Footnotes
    Support  The Glaucoma Foundation research grant, NIH grant EY017991 (V.S.), AHA Investigator Development Award # 0735014B and Fight For Sight (FFS) fellowship PD05034 (D.I.); and an unrestricted grant to the U
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 132. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      D. J. Barakat, G. Dvoriantchikova, D. Ivanov, R. Brambilla, V. I. Shestopalov; NF-kB Regulated Neurotoxicity of Reactive Astrocytes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):132.

      Download citation file:

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

  • Supplements

Purpose: : Astrocytes re-activate and exhibit abberant functions in response to injury and other stressors. Astrocyte reactivation correlates with inflammation and possibly contributes to the loss of retinal ganglion cells (RGCs) in pathological conditions. In this study we sought to examine the effect of targeted inactivation of a key pro-inflammatory transcription factor NF-ΚB in astrocytes on the survival of RGCs.

Methods: : We utilized a co-culture model of RGCs with astrocytes reactivated with cytokines or oxygenen/glucose deprivation (OGD) to mimic pathological conditions leading to degeneration. To obtain astrocyte-specific suppression of NF-kB , we isolated astrocytes from a GFAP-IkB-dn transgenic mouse where NF-ΚB is inactivated through over-expression of a dominant negative form of the NF-ΚB super-repressor (IkB-dn) under the control of the GFAP promoter. We compared neuronal survival co-cultured with IΚB-dn and WT astrocytes, treated with either TNFa or OGD.

Results: : In vitro reconstruction of glia-neuron interactions confirmed a neurotoxic effect induced by NF-kB in reactive astrocytes in vivo. Our data indicated that blocking the activation of astroglial NF-ΚB significantly reduced the expression of genes encoding NADPH-oxidase subunits, TNF and ICAM-1. In co-cultures of RGCs with either WT or IkB-DN astrocytes subjected to OGD, we observed significantly greater numbers of caspase-3 positive RGCs in co-culture with WT cells. Antioxidants partially blocked NF-kB-induced glial toxicity, suggesting that oxidative damage may represent the major facilitator of RGC death in both models. We had also observed a significant decrease in RGC loss in a mouse laser glaucoma model. These results provide a new insight into the contribution of cellular crosstalk to the pathogenesis of neuronal degeneration mediated by the NF-kB pathway in astrocytes.

Conclusions: : Our data indicate that inhibiting NF-ΚB in astrocytes results in neuroprotection against ocular hypertension injury, suggesting an active role for this cell population in the pathophysiology of retinal ischemia and glaucoma likely by inhibiting either inflammation or oxidative stress.

Keywords: astrocyte • oxidation/oxidative or free radical damage 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.