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.
In MS, the optic nerve is often the site of the first symptoms (called Optic Neuritis) and has advantages for study over other brain regions in having a simple, regular structure without nerve cell bodies (neurons).
The aim in this project is to analyse MS-affected optic nerves by staining the cells involved with repair of damaged nerve sheaths (remyelination) to try to find out why this process often fails in later phase MS. By understanding more about “remyelination failure” (lack of myelin sheaths surrounding nerve fibres despite the presence of significant numbers of the type of cells known to carry out repair), it is hoped that researchers can find a way to prevent it happening and therefore improve patient health outcomes.
During 2010, a comprehensive panel of markers were applied to tissue sections from MS-affected optic nerves including some where the damaged area (“lesion”) conformed to the description of “remyelination failure”. This has resulted in the detailed description of the repair status within each nerve segment (block) and the reliable identification of the different individual cell types involved. In particular, those cells known to be involved in myelin sheath repair have been targeted with a range of markers designed to reveal their maturity status and relationship to nearby nerve fibres. By comparing staining patterns in remyelination failure blocks with those in examples of apparently normal and successfully repaired optic nerve, information has been derived about the maturity stage or stages of these cells. Interestingly, this detailed “phenotyping” of repair cells may point to significant differences between lesions that more superficially appear similar.
Many current studies aimed at therapeutic enhancement of repair in MS assume that the cells involved in remyelination failure comprise a homogeneous population prevented from reaching full maturation due to the influence of inhibitory agents. Ongoing investigation is aimed at clarifying whether or not this is the case.
Updated: 06 January, 2009