Leukocytes as key players in optic nerve neuroinflammation

ARANDA, MARCOS L; ALTSCHULER, FLORENCIA; GONZÁLEZ FLEITAS, MARÍA F; GUERRIERI, DIEGO; DIEGUEZ, HERNÁN H; DORFMAN D; ROSENSTEIN, RUTH E

Córdoba

Congreso; XXXIII Congreso Anual SAN; 2018

Sociedad Argentina de Investigación en Neurociencias

P261.-Leukocytes as key players in optic nerve neuroinflammationMarcos L. Aranda1, Florencia Altschuler1 ,María F. González Fleitas1, Diego Guerrieri2, Hernán H. Dieguez1, Damián Dorfman1, Ruth E. Rosenstein11 Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina, CEFyBO, UBA/CONICET., 2 Laboratorio de inmunomoduladores y regeneración deórganos, Facultad de Medicina, CEFyBO, UBA/CONICETPresenting author: Marcos Aranda, marcos8877@gmail.com_________________________________________________________________________________________Optic neuritis (ON) is a condition involving primary inflammation, demyelination, and axonal injuryin the optic nerve which leads to retinal ganglion cell (RGC) loss, and a decrease in pupil lightreflex (PLR) and visual evoked potentials (VEPs). Neuroinflammatory diseases are characterized by disruption of the blood-brain barrier (BBB) and increased leukocyte infiltration. The aim of thepresent work was to analyze the involvement of cell infiltration on visual damage induced byexperimental ON. LPS or vehicle were injected into the optic nerve from adult male Wistar rats.BBB integrity was analyzed through Evans blue perfusion on WT-GFPþ/WT chimeric rats. At 6 hpost-LPS injection an increase in albumin-Evan's blue leakage and in optic nerve cellularity wereobserved. At 24 h post-injection, e-GFP(+) cells (likely macrophages and neutrophils) were identify in LPS-injected optic nerves. Experimental ON induced an increase in the chemokine CCL2- immunoreactivity. The injection of Bindarit (a CCL2 inhibitor) and bone marrow depletion (by gamma irradiaton) significantly prevented the effect of ON on PLR, VEP amplitude, and RGCnumber. In order to induce BBB breakdown, tissue plasminogen activator (tPA) was injected intothe optic nerve. tPA microinjection mimicked the effect of ON on PLR and RGC number. Theseresults indicate that BBB integrity loss and leukocyte recruitment plays a key role in the visualdamage induced by experimental ON.