Optic Neuritis: A Model for the Immuno-pathogenesis of Central Nervous System Inflammatory Demyelinating Diseases

Abstract

Evidence for the tenuous regulation between the immune system and central nervous system (CNS) can be found with examples of interaction between these organ systems gone awry. Multiple sclerosis (MS) is the prototypical inflammatory disease of the CNS and is characterized by widely distributed inflammatory demyelinating plaques that can involve the brain, spinal cord and/or optic nerves. Optic neuritis (ON), inflammatory injury of the optic nerve that frequently occurs in patients with MS, has been the focus of intense study in part given the readily accessible nature of clinical outcome measures. Exploring the clinical and pathological features of ON in relation to other inflammatory demyelinating conditions of the CNS, namely MS and neuromyelitis optica, provides an opportunity to glean common and distinct mechanisms of disease. Emerging data from clinical studies along with various animal models involving ON implicate innate and adaptive immune responses directed at glial targets, including myelin oligodendrocyte glycoprotein and aquaporin 4. Resolution of inflammation in ON is commonly observed both clinically and experimentally, but persistent nerve injury is also one emerging hallmark of ON. One hypothesis seeking evaluation is that, in comparison to other sites targeted in MS, the optic nerve is a highly specialized target within the CNS predisposing to unique immunologic processes that generate ON. Overall, ON serves as a highly relevant entity for understanding the pathogenesis of other CNS demyelinating conditions, most notably MS.

Optic Neuritis in Multiple Sclerosis—A Review of Molecular Mechanisms Involved in the Degenerative Process

“…Activated T cells mature and expand clonally before dividing into effector cells and migrating through the bloodstream to breach the blood–brain barrier (BBB). Endothelial cells in the CNS microvasculature contain adhesion molecules, which activated T cells can attach to and penetrate [ 3 , 18 ]. The release of cytokines and other proinflammatory mediators aggravates the inflammatory environment, attracting more immune cells to the CNS and eventually leading to demyelination [ 3 , 21 , 22 ].…”

“…Structural and functional abnormalities in the visual system are targeted in most patients with MS, typically at the earliest stages of the disease, defining a hallmark feature of MS, namely optic neuritis (ON). The evolution of the clinical picture of patients with MS is extremely variable and heterogeneous in terms of locations and extensions of brain and spinal cord lesions [ 3 ]. ON is an inflammatory injury of the optic nerve that leads to visual disability.…”

“…Clinical studies have demonstrated that ON and MS associate the same characteristics of inflammatory demyelination, the substrate being perivascular infiltrates that induce a significant cellular response that secondarily causes myelin damage in the nerve parenchyma. On the other hand, ON and MS associate distinct pathophysiological mechanisms that support CNS immune involvement [ 3 ].…”

Amnion-Derived Multipotent Progenitor Cells Suppress Experimental Optic Neuritis and Myelitis

“…1× AMP cells given by IV administration (N = 7), and 3× AMP cell treatments given by IP (N = 6) or IV (N = 9) injection all showed a significant (***p < 0.001) attenuation of EAE clinical scores as compared with vehicle-treated EAE mice, whereas 1× treatment with AMP cells by IP injection (N = 6) did not significantly reduce EAE scores. Data represent mean ± SEM and MS optic neuritis [34][35][36][37][38]. To evaluate inflammation in the optic nerve, control, EAE, and AMP cell-treated mice were sacrificed on day 42 p.i.…”

Functional evolution of visual involvement in experimental autoimmune encephalomyelitis

“… 5 Immunized C57BL/6 mice develop a chronic disease in which motor disability onset is generally around 14 dpi and ON is often detected. 6 It has been reported that in the optic nerve, where the volume to surface ratio of myelin is quite low, MOG expression is increased compared to other proteins such as proteolipid protein (PLP), which is concentrated on the compact myelin. 7 Functional damage of the anterior visual system can be detected with Visual Evoked Potential (VEP) and Electroretinogram (ERG), while Optical Coherence Tomography (OCT) is used to evaluate structural retinal alterations.…”