Abstract
Purpose: :
Autoantigens and autoantibodies play important roles in pathogenesis of autoimmune diseases, including autoimmune retinopathy and optic neuropathy. The goal of the study was to discover unique autoantibodies associated with neuroretinopathy and their antigenic targets in the optic nerve to better understand pathogenesis of the disease.
Methods: :
Autoantibodies against human optic nerve antigens were detected in sera of patients with neuroretinopathy by Western blotting, ELISA, proteomic analysis, and immunohistochemistry.
Results: :
Out of 212 patients tested for anti-optic nerve autoantibodies, 55% showed specific neuronal autoantibodies. The repertoire of anti-optic nerve autoantibodies often differed from anti-retinal autoantibodies. The major antigenic targets for these antibodies could be divided into four groups. Autoantibodies specific to classical glycolytic enzymes involved in energy production (α and γ enolases, glyceraldehyde 3-phosphate dehydrogenase) also reacted with retinal antigens.. However, autoantibodies targeted neuronal specific myelin proteins (MBP, MOG, PLP), aquaporins, and collapsing response mediator proteins seem to be specific for optic neuropathy. They immunostained axons and myelin in the optic nerve tissue as determined by IHC.
Conclusions: :
We identified novel neuronal autoantigens not previously known to be associated with neuroretinopathy. A direct role of specific autoantibody binding to proteins in optic nerve neurons may lead to apoptosis of cells, as well as inhibiting enzymes that preserve neuronal glycolytic activity and neuronal integrity. Knowledge of the full autoantibody repertoire perpetuating in neuroretinopathy is an important requirement in better understanding of the autoimmune process to facilitate better diagnosis, prognosis, and treatment.
Keywords: autoimmune disease • optic nerve • CAR