Electrophysiological analysis of factors involved in the primary demyelinating diseases: the rabbit eye model system

Abstract

This study explores the longitudinal assessment of visual evoked potentials (VEPs) in the rabbit as a method for defining factors underlying functional and structural changes associated with optic neuritis and the inflammatory demyelinating diseases. In rabbits with experimental autoimmune encephalomyelitis (EAE) induced by sensitization with guinea pig spinal cord myelin, injection of lymphokines into the posterior chamber of one eye (monocular challenge) produces an early inflammatory response in the retina and optic nerve, and an alteration in the VEP, all limited to the injected eye and its projections. The earliest changes in the timing and distribution of the cortical VEP occur within hours of ocular challenge and precede histopathological evidence of structural demyelination at the light microscope level. Prechallenge assessment allows the induced monocular prechiasmal effects to be distinguished from the more diffuse electrophysiological findings associated with EAE (i.e. those due to sensitization alone). In sensitized/challenged animals there is a clear correspondence between electrophysiological and morphological measures of dysfunction at the time points sampled. These results suggest that this model system afford an excellent opportunity to examine the precise structural correlates of the early functional changes associated with the onset of inflammatory demyelination within the CNS. Furthermore, the stability of the system provides the capacity to monitor alterations over the complete course of inflammation, demyelination and remyelination, induced by experimental manipulations.