Autoimmunity against neurofilament protein and its possible association with HLA-DRB1*1502 allele in glaucoma

Development of spontaneous optic neuropathy in NF‐κΒp50‐deficient mice: requirement for NF‐κΒp50 in ganglion cell survival

“…Several studies demonstrated that autoantibodies against RGCs participate in developing neuropathy in glaucoma patients [7–12]. Furthermore, recent reports show potential autoantibody production in p50‐deficient mice.…”

“…Glaucoma is understood to be a neurodegenerative disease, in which decreasing RGCs' survival results in visual field loss. In recent years, several lines of evidence have been rapidly accumulating that suggest that damage to the optic nerve may be caused by many risk factors, such as ischaemia, genetic background, glutamate and immune response, in addition to IOP [3–12]. Among these, glutamate is the main excitatory neurotransmitter in the retina as well as in the CNS.…”

“…Recent studies show the potential role of the immune system in the pathogenesis of glaucoma [7–12,53,54]. These studies demonstrate that autoantibodies against ocular antigens are up‐regulated in the serum of patients with glaucoma, such as heat‐shock proteins, rhodopsin, g‐enolase, glutathione‐S‐transferase, phosphatidylserine, glycosaminoglycans and neurofilaments [7–12]. Meanwhile, p50‐deficient mice exhibited multiple immune response defects in a non‐specific response to infection and in responses involving B lymphocytes [55,56].…”

“…Intraocular pressure (IOP) has been regarded as a major risk factor for developing glaucoma [1,2]; however, several lines of evidence have been gradually accumulating that suggest several risk factors such as ischaemia, glutamate and genetic background, which also play important roles in the development of glaucoma [3–6]. Furthermore, autoimmunity that directly recognizes retinal proteins has been associated with developing neuropathy in glaucomatous patients [7–12].…”

Vitreal IgM Autoantibodies Target Neurofilament Medium in a Spontaneous Model of Autoimmune Uveitis

“…42 Possessing posttranslational modifications, including glycosylations, 43,44 featuring a repetitive motif in its amino acid sequence, 44 and assembling to form polymeric repetitive filament structures, 41 NF-M may be fit to elicit a TI-2 response. Although it is the NF-L subunit, that has been described as a target for serum autoantibodies in glaucoma patients [45][46][47] and the neurofilament triplet has been shown to occasionally induce antibodies that cross-react among the subunits, 48,49 we confirmed by ELISA that vitreal IgM autoantibodies specifically target NF-M and do not react with NF-L. A TI-2-like activation of B cells by NF-M may thus explain the dominance, as well as the prolonged persistence, of IgM in the autoimmune response toward NF-M. The unique immunoregulatory microenvironment in the eye 50 may in some way influence B cells or plasma cells, as well, and further influence the response toward IgM domination, instead of switching to an IgG response.…”