April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Demyelinating Strain MHV-A59 Induces RGC Loss in Chronic Model of Optic Neuritis
Author Affiliations & Notes
  • Reas Sulaimankutty
    Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania
  • Zoe Fonseca-Kelly
    Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania
  • Kimberly Dine
    Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania
  • Jayasri D. Sarma
    Indian Institute of Science Education and Research, Kolkata, India
  • Mayssa Nassrallah
    Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania
  • Kenneth S. Shindler
    Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania
  • Footnotes
    Commercial Relationships  Reas Sulaimankutty, None; Zoe Fonseca-Kelly, None; Kimberly Dine, None; Jayasri D. Sarma, None; Mayssa Nassrallah, None; Kenneth S. Shindler, None
  • Footnotes
    Support  NIH Grants EY015098 and EY019014; Research to Prevent Blindness; and the F. M. Kirby Foundation
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4676. doi:
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      Reas Sulaimankutty, Zoe Fonseca-Kelly, Kimberly Dine, Jayasri D. Sarma, Mayssa Nassrallah, Kenneth S. Shindler; Demyelinating Strain MHV-A59 Induces RGC Loss in Chronic Model of Optic Neuritis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4676.

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

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Abstract

Purpose: : Optic neuritis (ON), an inflammatory demyelinating optic nerve disease, occurs in multiple sclerosis (MS). Pathological mechanisms and potential treatments for ON have been studied via experimental autoimmune MS models. Evidence suggests that virus-induced inflammation is a potential etiology triggering MS and ON; experimental virus-induced ON models are therefore required. We previously showed that MHV-A59, a mouse hepatitis virus (MHV) strain that causes brain and spinal cord inflammation and demyelination, induces ON by promoting inflammatory cell infiltration whereas MHV-2, a nondemyelinating MHV strain, does not induce ON. However, downstream effects on RGCs remains poorly understood. In the present study, we investigate effects of MHV-A59 and MHV-2 infection on RGC survival.

Methods: : RGCs are retrogradely-labeled with fluorogold by injection into superior colliculi. 4-5 week old C57/Bl6 mice are inoculated with plaque-purified MHV strains by intracranial injection one week later (day 0), using 50% of the lethal dose of MHV-A59 (2,000 PFU) or MHV-2 (50 PFU). Control mice are sham injected with PBS. Mice are sacrificed during acute infection, days 5-7, or during chronic demyelination, day 30. RGCs are quantified by counting fluorescent cells in 12 standardized fields of each isolated retina.

Results: : Inflammatory cell infiltration, consisting predominantly of macrophages, is detected by histologic evaluation in half of optic nerves from MHV-A59 infected mice at days 5 and 7, whereas less than 10% of optic nerves from MHV-2 infected mice develop inflammation. Three weeks later, during the chronic demyelinating phase of MHV infection, significant RGC loss is observed in eyes of mice infected with MHV-A59 (p<0.001) compared to control and MHV-2 infected mice. In contrast, MHV-2 infected mice show no significant RGC loss compared to controls.

Conclusions: : Experimental ON is an important model used to characterize neuronal damage and develop novel therapies for MS. The MHV-A59-induced ON model provides a critical adjunct to study the pathophysiology of ON secondary to virus-mediated inflammation, as this is one mechanism that may trigger ON and MS in patients. Importantly, our results demonstrate MHV-A59 causes RGC loss in this model of optic neuritis, suggesting this model can be used not only to study mechanisms of optic nerve inflammation and demyelination, but also mechanisms underlying neuronal damage and RGC loss.

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