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Originally published In Press as doi:10.1167/iovs.08-3211 on February 21, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:3275-3282.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-3211
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Optic Neuritis in Different Strains of Mice by a Recombinant HSV-1 Expressing Murine Interleukin-2

Mandana Zandian,1 Raelene Belisle,1 Kevin R. Mott,1 Steven Nusinowitz,2 Florence M. Hofman,3 and Homayon Ghiasi1

1From the Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Burns and Allen Research Institute, Los Angeles, California; the 2Department of Ophthalmology, UCLA School of Medicine, Los Angeles, California; and the 3Department of Pathology, USC School of Medicine, Los Angeles, California.

PURPOSE. The authors have shown previously that a recombinant HSV-1 that constitutively expresses two copies of murine IL-2 (HSV-IL-2) induces demyelination by activated CD8+ T cells in the brain and spinal cord of ocularly infected female BALB/c mice. The present study was conducted to determine whether the ocular infection with this recombinant virus induces optic neuritis independent of virus dose, major histocompatibility complex (MHC) background, or sex.

METHODS. Female BALB/c, C57BL/6, SJL/6, and 129SVE mice and male BALB/c mice were ocularly infected with different doses of recombinant HSV-IL-2 virus. Demyelination of optic nerves in infected mice was monitored histologically using Luxol fast blue staining and by measurement of visual-evoked cortical potentials (VECPs).

RESULTS. Both focal and diffuse regions of demyelination of the optic nerves were observed in the HSV-IL-2–infected mice as early as day 10 after infection and as late as day 60 after infection (the final experimental time point) in all strains of mice tested. Optic nerve demyelination was not observed in control mice ocularly infected with HSV-IL-4 or wild-type HSV-1. VECP responses were delayed significantly in the HSV-IL-2–infected mice compared with mice infected with control viruses.

CONCLUSIONS. The results demonstrate for the first time that a combination of viral infection and constitutive expression of IL-2, but not IFN-{gamma} or IL-4, can result in demyelination and visual impairment in the optic nerves of ocularly infected mice.






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