New perspectives in the therapeutics of optic neuritis

Abstract

Optic neuritis, the most common optic neuropathy affecting youngadults, is a condition involving primary inflammation, demyelination,and axonal injury of the optic nerve which leads to retinal ganglion celldeath and visual dysfunction. Clinical features of optic neuritis includeperi- or retro-ocular pain accentuated by eye movement, abnormal visualacuity and field, distorted color vision, afferent pupillary defect, andabnormal visual evoked potentials. Optic neuritis manifests as acute andsevere decreased vision for 1 - 2 weeks, which self-recovers over 1 - 3months in most of the patients; however, varying degree of permanentvisual dysfunction can occur in ~ 50% of patients. Even if visual acuityimproves, most patients have some residual visual function deficits.Moreover, repeated episodes of optic neuritis can result in optic nerveatrophy and permanent vision loss, which correlates with retinal ganglioncell loss. Optic neuritis has many causes; it may be related to a broadrange of autoimmune or infectious diseases, and it is closely associatedwith multiple sclerosis. On the other hand, acute optic neuritis oftenoccurs as an isolated clinical event, without contributory systemicabnormalities, and it is retrospectively diagnosed as idiopathic (orprimary) optic neuritis. Corticosteroids are the current mainstays oftherapy for the treatment of optic neuritis. However, though steroids canbe used to speed visual recovery, the overall visual improvement isunaffected by treatment. In fact, corticosteroids do not prevent axonalloss or improve visual outcome. Therefore, a key area of therapeuticresearch is to identify neuroprotective strategies that can prevent axonand retinal ganglion cell loss, and hopefully lead to better visualoutcomes. Neuroinflammatory diseases are characterized by blood-brainbarrier disruption and increased leukocyte infiltration. Circulatingleukocytes that migrate to sites of tissue injury and infection are keyplayers in inflammation by eliminating the primary inflammatory triggerand contributing to tissue repair. Nevertheless, it has been wellestablished that excessive or uncontrolled peripheral cell infiltration cancause enhanced tissue injury. In this chapter, we will discussexperimental data supporting the neuroprotective effect of two differenttherapeutic strategies for optic neuritis: i) the exposure to enrichedenvironment, and ii) a treatment with melatonin. In addition, we willdiscuss the concept that strategies aimed at reducing monocyterecruitment into the optic nerve may prove effective against primaryoptic neuritis-induced visual loss.