Critical role of monocyte recruitment in optic nerve damage induced by experimental optic neuritis

ARANDA, MARCOS L.; GONZALEZ FLEITAS M FLORENCIA; PIÑERO, GONZALO M; ROSENSTEIN, RUTH E; GUERRIERI, DIEGO; DORFMAN, DAMIÁN

Chicago

Congreso; Neuroscience 2019- Society for Neuroscience; 2019

Society for Neuroscience

Topic: C.07. Neurotoxicity/ Inflammation/ and NeuroprotectionSupport: Agencia Nacionalde Promoción Científica y Tecnológica PICT 1563, PICT 2731University of Buenos Aires (20020130100564)Consejo Nacional deInvestigaciones Científicas y T écnicas (PIP 0707)Title: Critical role of monocyte recruitment in optic nerve damage induced by experimental optic neuritisAuthors: *M. ARANDA1, D. GUERRIERI2, G. M. PIÑERO3, M. GONZÁLEZ FLEITAS4, D. DORFMAN5, R. E. ROSENSTEIN6; 1Northwestern Univ., Chicago, IL; 2CEFyBO, Buenos Aires, Argentina; 3Química Biológica Patológica, Facultad de Farmacia y Bioquímica, UBA, CABA, Argentina; 4Univ. of Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina; 5Sch. of Medicine, UBA, CEFYBO/CONICET, Capital Federal, Argentina; 6Human Biochem., Sch. of Medicine/Cefybo, Univ. of Buenos Ai, Buenos Aires, ArgentinaAbstract: Neuroinflammatory diseases are characterized by blood-brain barrier disruption (BBB) and leukocyte infiltration. We investigated the involvement of monocyte recruitment in visual pathway damage provoked by primary optic neuritis (ON) induced by a microinjection of bacterial lipopolysaccharide (LPS) into the optic nerve from male Wistar rats. Increased Evans blue extrava-sation and cellularity were observed at 6 h post-LPS injection. In WT-GFPþ/WTchimeric rat optic nerves, the presence of GFP(+) neutrophils and GFP(+) monocytes, and in wild-type rat optic nerves, an increase in CD11b+CD45lowand CD11b+CD45high cell number, were observed at 24 h post-LPS. Gamma-irradiation did not affect the increase in BBB permeability, but significantly lessened the decrease in pupil light reflex (PLR), and retinal ganglion cell (RGC) number induced by LPS. At 6 h post-LPS, an increase in chemokine (C-C motif) ligand 2 (CCL2) immunoreactivity co-localized with neutrophils (but not microglia/macrophages or astrocytes) was observed, while at 24 h post-injection, an increase in Iba-1-immunoreactivity and its co-localization with CCL2 became evident. The co-injection of LPS with bindarit (a CCL2 synthesis inhibitor) lessened the effect of LPS on PLR, and RGC loss. The treatment with etoposide or gadolinium chloride that significantly decreased peripheral monocyte (but not neutrophil or lymphocyte) percentage decreased the effect of LPS on PLR, and RGC number. Moreover, a negative correlation between PRL and monocyte (but not lymphocyte or neutrophil) percentage was observed at 7 days post-LPS. Taken together, these results support that monocytes are key players in the initial events that take place during primary ON.