Therapeutic effect of melatonin in an experimental model of optic neuritis

ARANDA ML; DIEGUEZ HH; DORFMAN D; SANDE PH; ROSENSTEIN RE

Seattle

Congreso; ARVO Annual Meeting 2016; 2016

Purpose: We have developed a new experimental modelof optic neuritis (ON) through the microinjection of bacteriallipopolysaccharide (LPS) into the optic nerve, which reproduces centralfeatures of human ON. The aim of this work was to analyze the effect ofmelatonin (MEL) on the optic nerve axoglial alterations induced by experimentalON. Methods: For this purpose, LPS (1 μl, 4.5 μg) wasinjected in one optic nerve from adult male Wistar rats, while thecontralateral optic nerve was injected with vehicle. One group of animalsreceived a subcutaneous pellet of MEL (20 mg) one day before LPS or vehicleinjection which was replaced at 15 days, and another group was submitted to asham procedure. In another set of experiments, the pellet of melatonin was implantedat 4 days post-injection of LPS or vehicle. The effect of melatonin wasanalyzed at 21 days post-injection in terms of: i) visual pathway function(visual evoked potentials (VEPs)), ii) anterograde transport from the retina tothe superior colliculus (intravitreal injection of cholera toxin β-subunit),iii) pupil light reflex (PLR), iv) microglia/macrophages (by Iba-1 and ED1immunoreactivity), v) astrocytes (by glial fibrillary acidprotein-immunostaining), vi) axon number (by toluidine blue staining), vii)demyelination (by luxol fast blue staining), viii) retinal ganglion cells(RGCs) number (by Brn3a immunoreactivity), and iv) optic nerve lipidperoxidation (TBARS). Results: LPS induced a significant decrease in VEPamplitude and PLR, a reduction in retinal anterograde transport, an increase inIba-1 and ED1 immunoreactivity, astrocytosis, demyelization, an increase inlipid peroxidation, and RGC loss. The pre-treatment with MEL significantlyprevented all these alterations. The post-treatment with MEL significantly preservedVEP amplitude and PLR. Conclusion: The treatment withmelatonin prevented functional and histological alterations and diminished thevulnerability of RGC to the deleterious effects of experimental ON, probablythrough an antioxidant mechanism. Therefore, these results indicate thatmelatonin could be a promissory resource in the management of ON.