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  • Neuroscience Seminar Series

    Friday, October 26th. 2018, 11:30 am, R229 (2rd Floor), Centre Universitaire des Saints-Pères, 45 rue des Saints-Pères, 75006 Paris

    Gordon Plant , Consultant Neurologist to the National Hospital for Neurology and Neurosurgery, Queen Square, Moorfields Eye Hospital, and the Medical Eye Unit, St Thomas’ Hospital, London

     

    Title: Fore and aft: the human visual pathway as a model for trans-synaptic (trans-neuronal) degeneration

     

    Summary:

    In the mid-19th Century the English scientist Augustus Waller studied distal (direct anterograde) axonal degeneration following damage to the hypoglossal nerve in animals. The technique was later used to map neuronal connections in the brain and consequently this specific consequence of focal damage to an axon acquired an eponym: “Wallerian” degeneration. Waller however also realized the significance of his finding in the study of neurological disease and the potential for remote effects of focal damage. Trans-synaptic (trans-neuronal) degeneration is more difficult to study because of the length of time required for the observed effects to occur. The visual pathway is a convenient system to study these classes of degeneration because the retinal ganglion cells can be directly observed in humans in life and the vast majority of their axons have a single synapse in the lateral geniculate nucleus with a neuron that projects to layer IV of striate cortex. John M van Buren (who later became a Miami Neurosurgeon) published in the 1960’s evidence for retrograde trans-synaptic degeneration in both primate and human histological studies. However, its occurrence in humans remained controversial because standard clinical methods of observing the inner retinal layers could not detect changes in lesions acquired after birth. A decade ago I suggested employing the technique of optical coherence tomography to study the retinal nerve fiber layer thickness in human cases of both congenital and acquired occipital damage retrograde trans-synaptic degeneration does occur. We also investigated the time course in both acute and chronic lesions. In the past 10 years there has been increasing interest in trans-synaptic degeneration in a variety of disorders including multiple sclerosis (MS). We have recently suggested that an inner retinal finding thought to be related to the pathology of MS may be a non-specific example of retrograde trans-synaptic degeneration affecting bipolar cells and that the abnormalities in the brain thought to be evidence for glaucoma being a more generalized neurodegenerative condition can be explained by retrograde trans-synaptic degeneration.

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