title: Experimental optic neuritis induced by the microinjection of lipopolysaccharide into the optic nerve.
abstract: Optic neuritis (ON) is a condition involving primary inflammation, demyelination, and axonal injury in the optic nerve which leads to retinal ganglion cell (RGC) loss, and visual dysfunction. We investigated the ability of a single microinjection 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 remained intact or were injected with vehicle or LPS. The effect of LPS was evaluated at several time points post-injection in terms of: i) visual pathway and retinal function (visual evoked potentials (VEPs) and electroretinograms, (ERGs), respectively), ii) anterograde transport from the retina to its projection areas, iii) consensual pupil light reflex (PLR), iv) optic nerve histology, v) microglia/macrophage reactivity (by Iba-1- and ED1-immunostaining), vi) astrocyte reactivity (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, without changes in the ERG. In addition, LPS induced 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.
authors: Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina/CEFyBO, Universidad de Buenos Aires/CONICET, Paraguay 2155, Buenos Aires, Argentina.
authors: Marcos L
authors: ML
authors: Aranda
authors: Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina/CEFyBO, Universidad de Buenos Aires/CONICET, Paraguay 2155, Buenos Aires, Argentina.
authors: Damián
authors: D
authors: Dorfman
authors: Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina/CEFyBO, Universidad de Buenos Aires/CONICET, Paraguay 2155, Buenos Aires, Argentina.
authors: Pablo H
authors: PH
authors: Sande
authors: Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina/CEFyBO, Universidad de Buenos Aires/CONICET, Paraguay 2155, Buenos Aires, Argentina. Electronic address: ruthr@fmed.uba.ar.
authors: Ruth E
authors: RE
authors: Rosenstein
mesh_terms: D000818:Animals; D002772:Cholera Toxin / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D005074:Evoked Potentials, Visual / Q000187:drug effects; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008845:Microinjections; D009900:Optic Nerve / Q000473:pathology*; D009902:Optic Neuritis / Q000134:cerebrospinal fluid / Q000139:chemically induced* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012025:Reflex, Pupillary / Q000187:drug effects; D012160:Retina / Q000473:pathology
chemical_list: D008070:Lipopolysaccharides; D002772:Cholera Toxin
keywords: Demyelination; Inflammation; Lipopolysaccharide; Neurodegeneration; Optic nerve; Optic neuritis; Pupil light reflex; Visual evoked potentials