Therapeutic benefit of environmental enrichment on optic neuritis.


Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine/CEFyBO, University of Buenos Aires/CONICET, Paraguay 2155, 5th Floor, 1121, Buenos Aires, Argentina. Electronic address: [Email]


Optic neuritis (ON) is an inflammatory, demyelinating, neurodegenerative, and presently untreatable condition of the optic nerve which might induce blindness. We analyzed the effect of environmental enrichment (EE) on visual pathway damage provoked by experimental ON induced by a microinjection of bacterial lipopolysaccharide (LPS) into the optic nerve. For this purpose, LPS was microinjected into the optic nerve from male Wistar rats. After injection, one group of animals was submitted to EE, and another group remained in standard environment (SE) for 21 days. EE prevented the decrease in pupil light reflex (PLR), visual evoked potentials, retinal anterograde transport, phosphorylated neurofilament immunoreactivity, myelination (luxol fast blue staining), and axon (toluidine blue staining) and retinal ganglion cell (Brn3a-immunoreactivity) number. EE also prevented microglial/macrophage reactivity (Iba-1- and ED1-immunoreactivity), and astrocytosis (glial fibrillary acidic protein-immunostaining) induced by experimental ON. LPS-injected optic nerves displayed oxidative damage and increased inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β and TNFα mRNA levels which were prevented by EE. EE increased optic nerve brain-derived neurotrophic factor levels. When EE started at 4 (but not 7) days post-injection of LPS, a preservation of the PLR was observed at 21 days post-LPS, which was blocked by the daily administration of ANA-12 from day 4 to day 7 post-LPS. Moreover, EE from day 4 to day 7 post-LPS significantly preserved the PLR at 21 days post-injection. Taken together, our data suggest that EE preserved visual functions and reduced neuroinflammation of the optic nerve. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment".


Environmental enrichment,Neuroinflammation,Optic neuritis,Retinal ganglion cells,