April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
The Role of Astroglial NADPH Oxidase in Retinal Ganglion Cell Survival
Author Affiliations & Notes
  • D. J. Barakat
    Molecular Cell and Developmental Biology,
    University of Miami, Miami, Florida
  • D. Ivanov
    Opthalmology,
    University of Miami, Miami, Florida
  • G. Dvoriantchikova
    Opthalmology,
    University of Miami, Miami, Florida
  • V. Shestopalov
    Opthalmology,
    University of Miami, Miami, Florida
  • Footnotes
    Commercial Relationships  D.J. Barakat, None; D. Ivanov, None; G. Dvoriantchikova, None; V. Shestopalov, None.
  • Footnotes
    Support  AHA Scientist Development Award 0735014B (D.I.); NIH grant EY017991 and a and The Glaucoma Foundation grant to (V.S.), and P30 EY014801
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5463. doi:
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      D. J. Barakat, D. Ivanov, G. Dvoriantchikova, V. Shestopalov; The Role of Astroglial NADPH Oxidase in Retinal Ganglion Cell Survival. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5463.

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

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Abstract

Purpose: : One of the known mechanisms of neuronal insult following ischemia is through oxidative damage. Astrocytes, the glial cells that support neuronal homeostasis and influence their survival to insults, undergo rapid activation after ischemia. Activated astrocytes have been shown to produce reactive oxygen species (ROS) via the activity of NADPH Oxidase. The aim of this study was to explore the regulatory mechanisms of NADPH Oxidase in astrocytes and its effects on retinal ganglion (RGC) survival after oxygen glucose deprivation.

Methods: : Astrocytes were obtained from WT and transgenic mice expressing the IkBα super repressor, and were challenged with OGD in a hypoxia chamber and switched to a glucose-free media for 4 hours. Changes in gene expression were analyzed by quantitative PCR, NADPH oxidase-dependent superoxide production by Diogenes assay, and cell death by activated caspase-3 immunohistochemistry.

Results: : Following OGD, astrocytes increased p47PHOX transcript levels in an NF-kB dependent manner. Analysis of the p47PHOX promoter suggested that an NF-kB binding site is critically important for p47PHOX promoter activity, implying a mechanism for transcriptional regulation. We found that transgenic suppression of the NF-kB via the activity of IkBα super repressor resulted in decreased activity of NADPH oxidase following OGD in primary astrocytes. This decrease correlated with lowered neurotoxicity to RGCs in co-cultures. Thus, co-cultures of retinal ganglion cells with the transgenic astrocytes showed decreased neuronal death when compared to those with the wild type astrocytes following OGD.

Conclusions: : Our findings revealed that a direct toxicity of astrocytes to retinal ganglion cells is mediated by NF-kB -dependent ROS production. This implies, that therapeutic strategies targeting NF-kB or it’s downstream effectors like NADPH oxidase, can be considered therapeutic targets for ischemic retinal diseases.

Keywords: astrocytes: optic nerve head • ischemia • oxidation/oxidative or free radical damage 
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