Abstract:

Acute optic neuritis (AON) is a common, and often the earliest manifestation of central nervous system (CNS) inflammatory demyelinating disorders like multiple sclerosis (MS) and neuromyelitis optica. It affects at least half the patients with MS and is the presenting feature in 15-20% of patients Several unique features of the afferent visual pathway (AVP) make the AON model an ideal system to study disease pathogenesis and evaluate potential neuroprotective and myelin repair strategies. Over the past decade, advancements in technology have made precise structural, functional and electrophysiological characterization of the AVP possible, using sensitive and largely non-invasive methods. These techniques, now validated, have confirmed correlation of structural, functional and electrophysiological measures of the AVP. Furthermore, investigations have established association of clinical and radiologic non-ocular disease activity in MS with accelerated loss of retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layers (GCIPL) of the retina, as measured by optical coherence tomography (OCT). Since, retinal changes in MS appear to reflect global CNS processes, it appears reasonable to generalize lessons learnt from the AVP to the CNS as a whole in CNS inflammatory demyelinating disorders. The presence of axons and glia in the absence of myelin is a feature unique to the retina in the CNS. This allows for independent monitoring of the derivative elements of CNS inflammatory injury; demyelination, axon loss and neuronal degeneration. Cases with relative axon preservation, ideal candidates for myelin repair, can be differentiated from those with axon involvement that require reconstitution of axon circuitry before myelin repair is attempted. Similarly, neuroprotective and even regenerative capabilities can be detected and monitored longitudinally using sensitive techniques to quantify RNFL and GCIPL thickness. In this article, we will describe the modern, high precision, para-clinical tools that enable precise structural, functional and electrophysiological analysis of the AVP. This is followed by a discussion of the current and potential future applications of novel technology to study putative neuroprotective and myelin repair strategies, in an attempt to identify agents that preserve and repair tissue architecture, electrophysiology, and ultimately function.