Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

Abstract

Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON) and is an initial symptom of multiple sclerosis (MS). Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC) loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG), were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM), a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®), a balanced mixture of fatty acids (FAs), counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role.

Further Evidence on Efficacy of Diet Supplementation with Fatty Acids in Ocular Pathologies: Insights from the EAE Model of Optic Neuritis

“…As shown by our previous and present results, diet supplementation with FAs efficiently counteracts the effects of MOG when its administration starts the day of immunization. This protocol is in line with previous studies in which diet supplements are given after the pathology has been induced by MOG [ 5 ] although, the possibility exists that the incorporation of FAs into the diet before MOG-induction may be viewed as a preventive measure. Indeed, recent epidemiologic studies have reported a decreased incidence of MS among individuals with high intake of PUFAs [ 38 , 39 , 40 ] although conflicting results on a possible relationship between PUFA intake and decreased MS risk are also reported [ 41 ].…”

“…In line with a previous study [ 5 ], 9 MOG-treated mice and nine controls received by oral gavage (starting from the day of immunization until the day 16 when the animals were sacrificed) a mixture of saturated and unsaturated FAs including 20% of saturated FAs, while 17.5% of unsaturated FAs. Of this mixture, 3.75 mg suspended in 200 μL of 10% sucrose in water were administered to the animals.…”

“…Of this mixture, 3.75 mg suspended in 200 μL of 10% sucrose in water were administered to the animals. The mixture composition was described previously [ 5 ].…”

“…Indeed, in a murine model of dry AMD [ 3 ], we recently demonstrated that diet supplementation with a calibrated mixture of the long chain omega 3 and omega 6 FAs drastically ameliorates complement-mediated effects, thus decreasing macrophage recruitment and the production of pro-inflammatory and angiogenic cytokines, which in turn improve degenerative events in the retina and the choroid [ 4 ]. In addition, using the experimental autoimmune encephalomyelitis (EAE) mouse model of optic neuritis, we found that daily gavage with a FAs mixture delays the onset of EAE and prevents, at least in part, the death of retinal ganglion cells (RGCs) through a major anti-inflammatory action [ 5 ]. This has been shown to occur without affecting the infiltration of macrophages in the retina thus eventually preserving their correct release of trophic and growth factors that are known to prevent optic nerve degeneration [ 6 ].…”

Matrine protects retinal ganglion cells from apoptosis in experimental optic neuritis

“…The death of RGCs has been considered the main cause of vision loss after an episode of ON (10,11). In the animal model of relapsing/remitting EAE, RGC apoptosis begins within a few days after onset of optic nerve in ammation (12,13), suggesting that axonal damage and cell loss are induced by optic nerve in ammation.…”