The relationship between optic neuritis and remyelination

Summary

Optic neuritis (ON) is a condition that causes visual loss and occurs as a common feature of MS. 40-75% of people with ON have been reported to eventually develop MS. The presence of typical magnetic resonance imaging (MRI) lesions in the brain at the time of ON is a strong risk factor for MS.

Prof Stuart Graham will establish the relationship between size of a lesion and its effect on nerve function. Prof Graham’s research will monitor recovery over time as a means for establishing any remyelination and will also provide a means to measure the protective effect of drug therapies.

ON is a frequent initial sign of MS and is often used as a model for studying the mechanisms of axonal loss and de/remyelination in MS. In contrast to many brain lesions, the effects of MS lesions on the optic nerve are clinically apparent and potentially measurable. The recovery phase of ON presents an opportunity to examine the processes of myelin destruction, repair and possible axonal degeneration.

Progress to Date

In this project, Prof Graham established a laboratory model of ON in the mouse and examined lesions in the visual pathway using visual evoked potentials (VEPs). VEPs measures the time that it takes for a visual stimulus to travel from the eye to the part of the brain which processes vision. When the myelin sheath is damaged, this amount of time increases. Prof Graham was able to measure both the level of demyelination and amount of damage to the nerve fibres in the visual pathway using VEPs. ‘These findings are very useful for clinical assessment of ON and for prognosis evaluation,’ said Prof Graham.

This work has generated two publications in scientific journals with another two underway. Prof Graham has also written a book chapter that is in press (publications underway are marked with asterisks below). This work was funded by an MS Research Australia incubator grant, which are short term grants awarded to researchers gathering preliminary data on a topic, in order to establish whether continued funding is warranted. Prof Graham expects this preliminary data to be useful to apply for a full MS Research Australia project grant in the future.

Prof Graham also works closely with Associate Professor Klistorner at the University of Sydney who has been working on measuring visual evoked potentials in people with optic neuritis. For details of progress made in Associate Professor Klistorner’s MS Research Australia-funded project click here. The two research programs complement each other and allow faster progress with different approaches to the same question.

Publications

Gupta VK, You Y, Klistorner A, Graham SL. (2011) Focus on molecules: Sphingosine 1 Phosphate (S1P). Exp Eye Res10.1016/j.exer.2011.09.023
You Y, Klistorner A, Thie J, Graham SL. (2011) Latency delay is a real measurement of demyelination in vivo in a rat model of optic neuritis. Invest Ophthalmol Vis Sci 52(9):6911-8
* You Y, Klistorner A, Thie J, Gupta VK, Graham SL. Axonal loss in a rat model of optic neuritis is closely correlated with visual evoked potential amplitudes using electroencephalogram based scaling. Invest Ophthalmol Vis Sci.
* You Y, Gupta VK, Klistorner A, Graham SL. Anterograde transynaptic degeneration along the visual pathway in a rat model of optic nerve axotomy. PLoS One
* You Y, Klistorner A, Graham SL. Visual evoked potential recording in rodents. In: Pilowsky PM (editor), Neuromethods. New York/Heidelberg: Springer (Book Chapter).