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Marcos Luis Aranda, Damian Dorfman, Hernan H Dieguez, Pablo Sande, Monica S Chianelli, Ruth E Rosenstein; Therapeutic effect of melatonin in an experimental model of optic neuritis.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5092.
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© ARVO (1962-2015); The Authors (2016-present)
We have developed a new experimental model of optic neuritis (ON) through the microinjection of bacterial lipopolysaccharide (LPS) into the optic nerve, which reproduces central 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 the contralateral optic nerve was injected with vehicle. One group of animals received a subcutaneous pellet of MEL (20 mg) one day before LPS or vehicle injection which was replaced at 15 days, and another group was submitted to a sham procedure. In another set of experiments, 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 pathway function (visual evoked potentials (VEPs)), ii) anterograde transport from the retina to the superior 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 glial fibrillary acid protein-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 lipid peroxidation (TBARS).
LPS induced a significant decrease in VEP amplitude and PLR, a reduction in retinal anterograde transport, an increase in Iba-1 and ED1 immunoreactivity, astrocytosis, demyelization, an increase in lipid peroxidation, and RGC loss. The pre-treatment with MEL significantly prevented all these alterations. The post-treatment with MEL significantly preserved VEP amplitude and PLR.
The treatment with melatonin prevented functional and histological alterations and diminished the vulnerability of RGC to the deleterious effects of experimental ON, probably through an antioxidant mechanism. Therefore, these results indicate that melatonin could be a promissory resource in the management of ON.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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