Identification of the cells responsible for nerve sheath repair in MS

The optic nerve connects the nerve cells of the eye to the brain and, in the human, contains about a million nerve fibres organised into parallel bundles. Despite its location, the optic nerve is considered a part of the brain. In multiple sclerosis (MS), the optic nerve is often the site of the first symptoms (called Optic Neuritis) that lead to diagnosis and most people living with MS experience Optic Neuritis at some stage. For the purpose of studying the underlying disease and repair processes of MS, the optic nerve has advantages over other brain regions in having a simple, regular structure and no nerve cell bodies (neurones).

In this study, MS-affected optic nerve specimens will be analysed by staining the cells involved with repair of damaged nerve sheaths (remyelination) to find out why this process fails in later phase MS. By understanding more about “remyelination failure” it is hoped that researchers can find a way to prevent it happening and therefore improve patient health outcomes.

Observations that oligodendrocyte lineage cells were present within some longstanding MS lesions have led to the concept of remyelination failure, whereby chronic demyelination is believed to be due to dysfunction of the repair pathway rather than absence of reparative cells per se. Stimulated by the prospect of therapeutic intervention to promote functional remyelination, the search for reasons behind remyelination failure forms a major focus in current MS research resulting in a range of hypotheses generated from numerous, predominately murine, experimental models.

The present project has direct relevance to MS through its potential to significantly improve knowledge about remyelination failure. By analysing (chronically) demyelinated MS lesions in the optic nerve (ON), where the regular architecture and relatively simple neuroglial complement provide advantages over other CNS tracts, it should be possible to provide a detailed description of the status of endogenous repair including the stage-specificity of oligodendrocyte lineage cells, from progenitor cells (OP) through to remyelinating oligodendrocytes. This accurate analysis of the cellular pathology of individual MSON lesions not only has the potential to further understanding of the disease process but will also allow experimentally-generated hypotheses of remyelination failure to be tested for validity.