May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Molecular Mechanism Underlying a Neuroprotective Effect of Low Dose -irradiation
Author Affiliations & Notes
  • L. Camras
    University of Nebraska Medical Center, Omaha, Nebraska
    Pharmacology and Experimental Neuroscience,
  • G. Labunskay
    University of Nebraska Medical Center, Omaha, Nebraska
    Pharmacology and Experimental Neuroscience,
  • C. B. Camras
    University of Nebraska Medical Center, Omaha, Nebraska
    Ophthalmology and Visual Sciences,
  • J. Kipnis
    University of Nebraska Medical Center, Omaha, Nebraska
    Pharmacology and Experimental Neuroscience,
    Ophthalmology and Visual Sciences,
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2491. doi:
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    • Get Citation

      L. Camras, G. Labunskay, C. B. Camras, J. Kipnis; Molecular Mechanism Underlying a Neuroprotective Effect of Low Dose -irradiation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2491.

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

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Abstract

Purpose:: Low-dose whole body γ-irradiation was shown to induce neuroprotection following optic nerve crush injury and recently under chronic neurodegenerative conditions in DBA/2J mice (mouse model for glaucoma). The neuroprotection was suggested to be mediated, at least in part, via activation of the immune system. Here we show a direct neuroprotective effect of irradiation via induction of neurotrophins and preservation of mitochondrial function in neurons.

Methods:: Primary neuronal cultures and neuronal cell line were used to investigate the neuroprotective mechanism induced by low-dose γ-irradiation (300 rad). Following irradiation, neuronal survival was assessed via TUNEL assay and neurotrophic factor expression and release was detected via immunohistochemical and ELISA methods. In the retina, levels of neurotrophic factors following irradiation were determined using western blots of retinal homogenates. Lastly, mitochondrial functions were studied using NADPH florescence with 2-photon microscopy.

Results:: Low dose γ-irradiation of neuronal cultures led to a significant decrease in percentage of TUNEL positive cells (40.0 ± 7.9% vs. 5.80 ± 1.8%, p < 0.001; intoxicated cells with vs. without irradiation, respectively). The neuroprotective effect of irradiation was inhibited by K252α, an inhibitor of neurotrophic factor receptors of Trk family (35.9 ± 6.9% vs. 35.0 ± 6.3%; p = 0.92). Irradiated in vitro neuronal cultures produced an increase in expression of several neurotrophic factors, including brain-derived neurotrophic factor (BDNF), which was in line with the increase in neurotrophin expression seen in retinas of irradiated mice. Additionally, γ-irradiation protected neurons from oxidative stress via a direct effect on mitochondria.

Conclusions:: These results suggest that neuroprotection induced by a low dose γ-irradiation is, at least in part, mediated via neurotrophic factors and preservation of mitochondrial functions, which may lead to the development of new therapeutic modalities for glaucoma, macular degeneration, and other neurodegenerative conditions.

Keywords: neuroprotection • ganglion cells • retinal degenerations: cell biology 
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