NEU1 is more abundant in uveitic retina with concomitant desialylation of retinal cells

Desialylation of cell surface glycoproteins carried out by sialidases affects various immunological processes. However, the role of neuraminidase 1 (NEU1), one of the four mammalian sialidases, in inflammation and autoimmune disease is not completely unraveled to date. In this study, we analyzed the retinal expression of NEU1 in equine recurrent uveitis (ERU), a spontaneous animal model for autoimmune uveitis. Mass spectrometry revealed significantly higher abundance of NEU1 in retinal Muller glial cells (RMG) of ERU-diseased horses compared to healthy controls. Immunohistochemistry uncovered NEU1 expression along the whole Muller cell body in healthy and uveitic states and confirmed higher abundance in inflamed retina. Muller glial cells are the principal macroglial cells of the retina and play a crucial role in uveitis pathogenesis. To determine whether higher expression levels of NEU1 in uveitic RMG correlate with the desialylation of retinal cells, we performed lectin-binding assays with sialic acid-specific lectins. Through these experiments, we could demonstrate a profound loss of both alpha 2-3- and alpha 2-6-linked terminal sialic acids in uveitis. Hence, we hypothesize that the higher abundance of NEU1 in uveitic RMG plays an important role in the pathogenesis of uveitis by desialylation of retinal cells. As RMG become activated in the course of uveitis and actively promote inflammation, we propose that NEU1 might represent a novel activation marker for inflammatory RMG. Our data provide novel insights in the expression and implication of NEU1 in inflammation and autoimmune disease.

Automated summary

This study found that in equine recurrent uveitis, NEU1 is expressed at higher levels in the retina, leading to desialylation of retinal cells and promoting the inflammatory process. NEU1 may serve as a novel activation marker for inflammatory retinal Muller glial cells in uveitis. These findings provide new insights into the role of NEU1 in inflammation and autoimmune disease.