Primary optic neuritis: involvement of monocyte recruitment in visual damage

Abstract

Optic neuritis, the most common optic neuropathy affecting youngadults, is a condition involving primary inflammation, demyelination, and axonal injury in the optic nerve which leads to retinal ganglion cell deathand visual dysfunction. Clinical features of optic neuritis include peri- orretro-ocular pain accentuated by eye movement, abnormal visual acuityand field, distorted color vision, afferent pupillary defect, and abnormalvisual evoked potentials. Optic neuritis manifests as acute and severedecreased vision for 1-2 weeks, then self-recovers over 1-3 months inmost of the patients; however, varying degree of permanent visualdysfunction 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 vision loss, which correlates with retinal ganglion cell loss.Optic neuritis has many causes; it may be associated to a broad range ofautoimmune or infectious diseases, and it is closely associated withmultiple sclerosis. On the other hand, acute optic neuritis often occurs asan isolated clinical event, without contributory systemic abnormalities,and it is retrospectively diagnosed as idiopathic (or primary) opticneuritis. Recently, we have developed a new experimental model ofprimary optic neuritis in rats through a single microinjection of bacteriallipopolysaccharide directly into the optic nerve, which mimics centralfeatures of the human disease. Neuroinflammatory diseases arecharacterized blood-brain barrier disruption and increased leukocyteinfiltration. Circulating leukocytes that migrate to sites of tissue injuryand infection are key players in inflammation by eliminating the primaryinflammatory trigger and contributing to tissue repair. Nevertheless, it hasbeen well established that excessive or uncontrolled peripheral cellinfiltration can cause enhanced tissue injury. In this chapter, we willdiscuss evidence supporting that monocytes are key players in the initialevents that take place during primary optic neuritis. Therefore, strategiesaimed at reducing monocyte recruitment into the optic nerve may proveeffective against primary optic neuritis-induced visual loss.