April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Effects of Corticosteroids in Experimental Optic Neuritis
Author Affiliations & Notes
  • M. Dutt
    Ophthalmology, University of Pennsylvania, Philadelphia,, Pennsylvania
  • P. Tabuena
    Neurology, Thomas Jefferson University, Philadelphia,, Pennsylvania
  • E. Ventura
    Neurology, Thomas Jefferson University, Philadelphia,, Pennsylvania
  • A. Rostami
    Neurology, Thomas Jefferson University, Philadelphia,, Pennsylvania
  • K. Shindler
    Ophthalmology, University of Pennsylvania, Philadelphia,, Pennsylvania
  • Footnotes
    Commercial Relationships  M. Dutt, None; P. Tabuena, None; E. Ventura, None; A. Rostami, None; K. Shindler, None.
  • Footnotes
    Support  NIH/ NEI grant no. KO8EY15098, Career Development Award from RPB, F.M. Kirby Foundation
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 1445. doi:
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    • Get Citation

      M. Dutt, P. Tabuena, E. Ventura, A. Rostami, K. Shindler; Effects of Corticosteroids in Experimental Optic Neuritis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1445.

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

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Abstract

Purpose: : Optic neuritis (ON) occurs with a high incidence in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). ON begins 9 days after immunization to induce EAE. Significant retinal ganglion cell (RGC) loss occurs in eyes with ON and is not detected until 14 days after immunization, suggesting that loss of RGCs is secondary to optic nerve inflammation. Treatment with corticosteroids suppresses RGC loss if administered daily beginning from day of immunization (d0) prior to disease onset. Our aim was to determine whether corticosteroid treatment is also effective at a clinically relevant time point after inflammation of the optic nerve begins.

Methods: : Stereotactic surgery with Fluorogold was used to retrogradely label RGCs. Proteolipid protein peptide 139-151 was injected to induce EAE and mice were scored daily for clinical EAE on a 5 point scale. Mice were treated daily from d0 to d14 or d10 to d14 with 200 mg/kg subcutaneous dexamethasone (dex), 20 mg/kg intraperitoneal methylprednisolone (MP) or PBS (control). Fluorescence microscopy was used to count labeled RGCs in retinal mounts and H&E staining was used to identify inflammatory infiltrates in the optic nerves.

Results: : Corticosteroid treatment from d0 to d14 almost completely blocked EAE, where PBS-treated mice developed typical EAE with an average score of 1.5 by d14. Less than 5% of eyes had ON when treated with dex from d0-d14 compared to more than 60% when treated with PBS and dex-treated eyes had significantly increased (>30%) RGC survival. Treatment with either dex or MP from d10-d14 led to only partial suppression of clinical EAE. Corticosteroid treatment beginning from d10 did not significantly reduce the presence of optic nerve inflammation at d14 or 18, nor did it enhance survival of RGCs.

Conclusions: : These experiments indicate that corticosteroid treatment in EAE mice initiated after inflammation has begun is not as effective when administered before the onset of ON. This is consistent with clinical outcomes in ON patients where MP treatment does not affect final visual outcome. This model can be used to evaluate potential alternative therapies to prevent RGC loss and permanent vision loss from ON.

Keywords: neuro-ophthalmology: optic nerve • neuroprotection • ganglion cells 
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