Neuroprotective effect of melatonin in experimental optic neuritis in rats

Abstract

Optic neuritis (ON) is an inflammatory, demyelinating, and neurodegenerative condition of the optic nerve, which might induce permanent vision loss. Currently, there are no effective therapies for this disorder. We have developed an experimental model of primary ON in rats through a single microinjection of 4.5 μg of bacterial lipopolysaccharide (LPS) into the optic nerve. Since melatonin acts as a pleiotropic therapeutic agent in various neurodegenerative diseases, we analyzed the effect of melatonin on LPS-induced ON. For this purpose, LPS or vehicle were injected into the optic nerve from adult male Wistar rats. One group of animals received a subcutaneous pellet of 20 mg melatonin at 24 hr before vehicle or LPS injection, and another group was submitted to a sham procedure. Melatonin completely prevented the decrease in visual evoked potentials (VEPs), and pupil light reflex (PLR), and preserved anterograde transport of cholera toxin β-subunit from the retina to the superior colliculus. Moreover, melatonin prevented microglial reactivity (ED1-immunoreactivity, P < 0.01), astrocytosis (glial fibrillary acid protein-immunostaining, P < 0.05), demyelination (luxol fast blue staining, P < 0.01), and axon (toluidine blue staining, P < 0.01) and retinal ganglion cell (Brn3a-immunoreactivity, P < 0.01) loss, induced by LPS. Melatonin completely prevented the increase in nitric oxide synthase 2, cyclooxygenase-2 levels (Western blot) and TNFα levels, and partly prevented lipid peroxidation induced by experimental ON. When the pellet of melatonin was implanted at 4 days postinjection of LPS, it completely reversed the decrease in VEPs and PLR. These data suggest that melatonin could be a promising candidate for ON treatment.

Dietary Sources and Bioactivities of Melatonin

“…The mechanism might be preventing the decrease in visual evoked potentials (VEPs) and pupil light reflex (PLR), inhibiting microglial reactivity, astrocytosis, demyelination, and axon and retinal ganglion cell loss and preserving anterograde transport of cholera toxin β-subunit from the retina to the superior colliculus. In the same study, the therapeutical effects of melatonin on ON was also observed as it reversed the decrease in VEPs and PLR completely when the pellet was implanted at 4 days postinjection of LPS [299]. …”

Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of HIF‐1α‐VEGF pathway in oxygen‐induced retinopathy mice

“…Besides, more and more studies had focused on the therapeutic effect for ophthalmic diseases. Some showed that melatonin played a neuroprotective role in glaucoma patients, animal models of retinitis pigmentosa and optic neuritis . It is also suggested to possess antioxidant properties and decrease the level of prostaglandins in experimental feline uveitis .…”

The role and therapeutic potential of melatonin in age‐related ocular diseases

“…Additionally, and in experimental models of optic neuritis and retinal ischemia, melatonin treatment inhibits glial reactivity and reduces the expression of hypoxia inducible factor ‐1α, COX‐2, and TNF‐α genes (Figure ) . It is, thereby, also acting as a neuroprotective agent.…”