How might demyelinating disorders and glaucoma modify synaptic function?

Latencies of visually evoked potentials (VEPs) tend to be abnormally long in multiple sclerosis (MS). Similar VEP delays are seen in glaucoma. Such delays could result in part from reduced intensities of synaptic inputs at post-retinal synaptic relays, and defects of axoplasmic transport might be one cause for this. The effective rate of synaptic activation of a given postsynaptic neuron can be decreased either by reducing the arrival-rate of presynaptic action potentials (e.g., by complete or partial blockage of conduction in some presynaptic axons), or by reducing the quantity of neurotransmitter released per action potential (e.g., as a consequence of presynaptic neurotransmitter depletion). It is proposed that in both glaucoma and MS, delayed VEPs may result from either or both of these mechanisms. Firstly, loss and functional impairment of optic nerve axons occurs in each disorder. Secondly, in glaucoma the increased intraocular pressure tends to block the rapid anterograde axoplasmic transport (RAAT) which brings neurotransmitter supplies to the axon terminals. This could result in neurotransmitter depletion in the lateral geniculate relay, decreased synaptic effectiveness of remaining normally-conducting optic nerve axons, and thereby increased VEP latencies. RAAT is also blocked by demyelinated lesions that have been produced experimentally by injection of diphtheria toxin. If it is impaired by the demyelinated plaques of multiple sclerosis, then VEP slowing by a similar presynaptic depletion mechanism could ensue.