Neuroprotective effect of melatonin in experimental optic neuritis in rats

ARANDA ML; GONZÁLEZ FLEITAS MF; KELLER SARMIENTO MI; DORFMAN D; SANDE PH; CHIANELLI MS; ROSENSTEIN RE

San Diego, CA, USA

Congreso; Neuroscience 2016, SfN; 2016

Society for Neuroscience

Poster424. Neuroprotection in Models of Immune Mediated DemyelinationLocation: Halls B-HTime: Monday, November 14, 2016, 1:00 PM - 5:00 PMProgram#/Poster#: 424.02/FF7Topic: C.06. Neurotoxicity, Inflammation, and NeuroprotectionSupport: ANPCyT - PICT 1563CONICET - PIP 0446Title: Neuroprotective effect of melatonin in experimental optic neuritis in ratsAuthors: *M. L. ARANDA, M. F. GONZALEZ FLEITAS, M. I. KELLER SARMIENTO, M.S. CHIANELLI, P. H. SANDE, D. DORFMAN, R. E. ROSENSTEIN;CEFyBO - CONICET, Buenos Aires, ArgentinaAbstract: We have developed a new experimental model of optic neuritis (ON) through themicroinjection of bacterial lipopolysaccharide (LPS) into the optic nerve, which reproducescentral features of human ON. The aim of this work was to analyze the effect of melatonin(MEL) on the optic nerve axoglial alterations induced by experimental ON. For this purpose,LPS (1 μl, 4.5 μg) was injected in one optic nerve from adult male Wistar rats, while thecontralateral optic nerve was injected with vehicle. One group of animals received asubcutaneous pellet of MEL (20 mg) one day before LPS or vehicle injection which wasreplaced at 15 days, and another group was submitted to a sham procedure. In another set ofexperiments, the pellet of melatonin was implanted at 4 days post-injection of LPS or vehicle.The effect of melatonin was analyzed at 21 days post-injection in terms of: i) visual pathwayfunction (visual evoked potentials (VEPs)), ii) anterograde transport from the retina to thesuperior colliculus (intravitreal injection of cholera toxin β-subunit), iii) pupil light reflex (PLR),iv) microglia/macrophages (by Iba-1 and ED1 immunoreactivity), v) astrocytes (by glialfibrillary acid protein-immunostaining), vi) axon number (by toluidine blue staining), vii)demyelination (by luxol fast blue staining), viii) retinal ganglion cells (RGCs) number (by Brn3aimmunoreactivity), and iv) optic nerve lipid peroxidation (TBARS). LPS induced a significantdecrease in VEP amplitude and PLR, a reduction in retinal anterograde transport, an increase inIba-1 and ED1 immunoreactivity, astrocytosis, demyelization, an increase in lipid peroxidation,and RGC loss. The pre-treatment with MEL significantly prevented all these alterations. Thepost-treatment with MEL significantly preserved VEP amplitude and PLR. The treatment withmelatonin prevented functional and histological alterations and diminished the vulnerability ofRGC to the deleterious effects of experimental ON, probably through an antioxidant mechanism.Therefore, these results indicate that melatonin could be a promissory resource in themanagement of ON.Disclosures: M.L. Aranda: None. M.F. Gonzalez Fleitas: None. M.I. Keller Sarmiento:None. M.S. Chianelli: None. P.H. Sande: None. D. Dorfman: None. R.E. Rosenstein: None.