Projects
Despite observations made by Ramon y Cajal over 100 years ago that neurons were damaged in Multiple Sclerosis (MS), most research has focused on the immune response, where an autoimmune attack against myelin, the protective glial covering of axons, results in the disruption of neuronal signalling. However, recent evidence has demonstrated that the degeneration of neurons and their axons, and not just the myelin sheath, does play a significant role in MS, where it may be the underlying cause of the clinical progression of the disease.
Our lab employs an animal model of MS, MOG-induced experimental autoimmune encephalomyelitis (EAE), to study the mechanisms underlying neurodegeneration. This model is useful since it results in a degeneration of the retinal ganglion cells (RGCs), the cells that form the axons of the optic nerve, resulting in optic neuritis. Optic neuritis is one of the most common clinical manifestations of MS, and can be studied in animal models through a combination of electrophysiological and histopathological methods. In our lab, we have shown that RGC degeneration starts very early during the disease course of optic neuritis. Interestingly, this is before major damage of the myelin sheath is observable suggesting that neurodegenerative processes are initiated prior to significant myelin attack.
The aim of our lab is to investigate the mechanisms underlying neurodegeneration of RGCs, and use this knowledge to develop methods to protect neurons from death during the progression of MS.
Histopathological analysis of optic nerve sections from Brown Norway rats during MOG-EAE. (A, B) Haemotoxylin-eosin staining shows an infiltration of immune cells into the optic nerve between day 5 post-immunisation (A) and day 8 of EAE (B). (C, D) Luxol fast blue staining demonstrates significant loss of myelin between day 5 post-immunisation (C) and day 8 of EAE (D). (E, F) Axonal loss can be seen with Bielschowsky silver impregnation between day 5 post-immunisation (E) and day 8 of EAE (F). Insets show higher magnification views.