Intracranial Inoculation Is More Potent Than Intranasal Inoculation for Inducing Optic Neuritis in the Mouse Hepatitis Virus-Induced Model of Multiple Sclerosis

Singh, Manmeet; Khan, Reas S.; Dine, Kimberly; Das Sarma, Jayasri; Shindler, Kenneth S.

Intranasal administration provides a potential non-invasive method for delivering material to the CNS. Interestingly, complex mixtures containing physiologic concentrations of multiple proteins show that protein can rapidly accumulate in the eye and optic nerve following intranasal delivery, suggesting a direct nose to eye diffusion pathway that remains to be fully elucidated (Khan et al., 2017) . The current results show that RSA59 does not follow a similar pattern of accumulation in the optic nerve, suggesting that viral particle may be too large or complex to follow the same pathway, or may actively enter neurons locally and restrict their movement to intraneuronal axonal transport. Nonetheless, the ability of neurotropic MHV viruses to infect different cells, translocate throughout the CNS, and induce inflammatory demyelination, continues to provide a reproducible model to study optic nerve and spinal cord demyelinating disease following intracranial inoculation. Thus, intracranial inoculation should continue to be considered a preferred method for studies of MHV-induced optic neuritis and CNS demyelinating disease.