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Melanie J Murphy, Sheila Gillard Crewther, Zhenjiang Li, Finn Connell, Jacqueline M Orian; Early Retinal Dysfunction in the Mouse EAE Model of Multiple Sclerosis: An Electrophysiological Characterisation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1877.
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© ARVO (1962-2015); The Authors (2016-present)
Multiple Sclerosis (MS) is a debilitating autoimmune disease that targets the central nervous system (CNS) and is increasing in incidence worldwide. The disease manifests in young adults with dysfunction within the visual system often the earliest indication of disease, making understanding the timeline and trajectory of changes in the retina a research priority. Thus, we investigated the temporal trajectory of electrophysiological changes in retinal function prior to, and after the presentation of clinical MS-like motor symptoms in the experimental autoimmune encephalomyelitis (EAE) mouse model of progressive MS.
EAE was induced in C57Bl/6 mice at 9 weeks of age via immunization with active myelin-oligodendrocyte-glycoprotein (MOG). Sham injections of inactive MOG were performed in a separate group of mice at the same age, and a non-treated control group was also included. Following general anaesthesia, retinal function was assessed via electroretinography (ERG) in all mice at day 9 or day 14 post MOG-injection. ERGs were collected in response to a square-wave flash of three light phase durations (0.1 msec, .01 msec and .001 msec) at a frequency of 1 Hz generated by a 150mm Ganzfeld stimulator. Signals were recorded via Powerlab amplifier (ADI, Sydney, Australia) and band-pass filtered (0.3-1000Hz). Following recordings, retinal and CNS tissue was collected for immunohistochemical analysis.
Although clinical MS-like motor symptoms were not apparent in MOG mice at day 9 post-EAE injection, hind limb weakness was apparent by day 14. No motor deficits were observed in Sham or control mice. Differences in ERG waveform latency, duration and amplitude were observable both at day 9 and day 14 post-EAE injection in comparison to Sham/control groups.
ERG results show reduced retinal function occurring notably earlier than gross motor deficits in the EAE mouse model of MS, suggesting that the high energy requirements of the retina may provide insight into the development and prediction of the progression of sites of disease. This potentially provides a strategic mechanism for early therapeutic intervention.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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