May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Inactivation of Astroglial NF-kB Reduces RGC Loss in Optic Neuritis in EAE Model
Author Affiliations & Notes
  • V. I. Shestopalov
    Univ of Miami Miller Sch of Med, Miami, Florida
    Bascom Palmer Eye Institute, Department of Cell Biology and Anatomy,
    University of Miami Miller School of Medicine, Miami, Florida
  • G. Dvoriantchikova
    Univ of Miami Miller Sch of Med, Miami, Florida
    Bascom Palmer Eye Institute, Department of Cell Biology and Anatomy,
  • D. Ivanov
    Univ of Miami Miller Sch of Med, Miami, Florida
    Bascom Palmer Eye Institute, Department of Cell Biology and Anatomy,
    Vavilov Institute of General Genetics RAS, Moscow, Russian Federation
  • R. Brambilla
    Univ of Miami Miller Sch of Med, Miami, Florida
    The Miami Project to Cure Paralysi, Department of Microbiology and Immunology,
  • J. R. Bethea
    Univ of Miami Miller Sch of Med, Miami, Florida
    The Miami Project to Cure Paralysi, Department of Microbiology and Immunology,
    The Miami Project to Cure Paralysis Dept. Neurology,
    University of Miami Miller School of Medicine, Miami, Florida
  • Footnotes
    Commercial Relationships  V.I. Shestopalov, None; G. Dvoriantchikova, None; D. Ivanov, None; R. Brambilla, None; J.R. Bethea, None.
  • Footnotes
    Support  NIH grant EY017991, TGF research grant, RPB Career Development Award (V.S.), AHA Award 0735014B , FFS fellowship PD05034 toD.I.; NIH grant NS051709 to JRB and NIH center grant P30 EY014801 to BPEI
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 791. doi:https://doi.org/
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    • Get Citation

      V. I. Shestopalov, G. Dvoriantchikova, D. Ivanov, R. Brambilla, J. R. Bethea; Inactivation of Astroglial NF-kB Reduces RGC Loss in Optic Neuritis in EAE Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):791. doi: https://doi.org/.

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

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Abstract

Purpose: : In the central nervous system (CNS) activation of the transcription factor NF-ΚB, a key regulator of inflammation and secondary injury processes, leads to both protective and detrimental effects on CNS after injury. Here we sought to examine the effect of targeted inactivation of NF-ΚB in astrocytes, glial cells known to play both proinflammatory neurodistructive and trophic neuroprotective roles in CNS injury, on optic nerve and retina pathology in experimental autoimmune encephalomyelitis (EAE).

Methods: : We employed a transgenic GFAP-IΚBα-dn (IΚBα-dn) mouse where NF-ΚB is specifically inactivated in astrocytes through overexpression of a dominant negative form of the NF-ΚB super-repressor under the control of the GFAP promoter. We induced EAE in IΚBα-dn mice and WT littermates and compared retinal ganglion cell loss and optic nerve pathology between the two strains.

Results: : Our data indicated that blocking the activation of astroglial NF-ΚB significantly reduces disease severity and improves functional recovery following EAE. The results of our analyses showed significant protection of RGCs in transgenic animals, which correlated with better morphology of these cells. At 80 days post injury (dpi), the neuronal density in the ganglion cell layer of WT retinas was reduced to about 50% of the number measured in naïve animals, while in IΚBα-dn mice the loss was limited to 19%. Interestingly, immunohistochemical studies showed an increased infiltration of blood leukocytes into the retina and optic nerve of the transgenic animals compared to WT at 80 dpi. Gene expression data indicate that the neuroprotective effects of astroglial NF-ΚB inactivation were likely due to lower levels of inflammation: chemokines, cytokines and other inflammatory molecules were decreased in IΚBα-dn mice compared to WT animals.

Conclusions: : Our data indicate that inhibiting NF-ΚB in astrocytes results in neuroprotective effects following EAE, suggesting an active role for this cell population in the pathophysiology of this disease.

Keywords: astrocyte • optic nerve • ganglion cells 
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