Development of a new experimental model of primary optic neuritis

ARANDA ML; DORFMAN D; SANDE PH; ROSENSTEIN RE

Mar del Plata

Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2015

Optic neuritis (ON) involves inflammation, demyelination, axonal injury in the optic nerve, retinal ganglion cell (RGC) loss, and visual dysfunction. We investigated the ability of a single injection of bacterial lipopolysaccharide (LPS) directly into the optic nerve to induce functional and structural alterations compatible with ON. For this purpose, optic nerves from male Wistar rats were injected with vehicle or LPS. At several time points post-injection, we analyzed: i) visual pathway function (visual evoked potentials (VEPs), ii) anterograde transport from the retina to its projection areas, iii) consensual pupil light reflex (PLR), iv) optic nerve structure, v) microglia/macrophage (by Iba-1- and ED1-immunostaining), vi) astrocytes (by glial fibrillary acid protein-immunostaining), vii) axon number (by toluidine blue staining), vii) demyelination (by myelin basic protein immunoreactivity and luxol fast blue staining), viii) optic nerve ultrastructure, and ix) RGC number (by Brn3a immunoreactivity). LPS induced a significant and persistent decrease in VEP amplitude and PLR, a deficit in anterograde transport, and an early inflammatory response consisting in an increased cellularity, and Iba-1 and ED1-immunoreactivity in the optic nerve, which were followed by changes in axonal density, astrocytosis, demyelination, and axon and RGC loss. These results suggest that the microinjection of LPS into the optic nerve may serve as a new experimental model of primary ON.