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

Abstract

In the experimental autoimmune encephalomyelitis (EAE) mouse model of optic neuritis, we recently demonstrated that diet supplementation with a balanced mixture of fatty acids (FAs), including omega 3 and omega 6, efficiently limited inflammatory events in the retina and prevented retinal ganglion cell (RGC) death, although mechanisms underlying the efficacy of FAs were to be elucidated. Whether FAs effectiveness was accompanied by efficient rescue of demyelinating events in the optic nerve was also unresolved. Finally, the possibility that RGC rescue might result in ameliorated visual performance remained to be investigated. Here, the EAE model of optic neuritis was used to investigate mechanisms underlying the anti-inflammatory effects of FAs, including their potential efficacy on macrophage polarization. In addition, we determined how FAs-induced rescue of RGC degeneration was related to optic nerve histopathology by performing ultrastructural morphometric analysis with transmission electron microscopy. Finally, RGC rescue was correlated with visual performance by recording photopic electroretinogram, an efficient methodology to unravel the role of RGCs in the generation of electroretinographic waves. We conclude that the ameliorative effects of FAs were dependent on a predominant anti-inflammatory action including a role on promoting the shift of macrophages from the inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype. This would finally result in restored optic nerve histopathology and ameliorated visual performance. These findings can now offer new perspectives for implementing our knowledge on the effectiveness of diet supplementation in counteracting optic neuritis and suggest the importance of FAs as possible adjuvants in therapies against inflammatory diseases of the eye.

A Novel HIF Inhibitor Halofuginone Prevents Neurodegeneration in a Murine Model of Retinal Ischemia-Reperfusion

“…Ellagitannins extracts from pomegranate flesh change the activity of protein disulfide-isomerase A3 (PDIA3) protecting the brain tissue from neurodegeneration involved in AD or PD [29]. Additionally, fatty acids in foods, especially omega-3 and -6, prevented RGC death caused by optic neuritis in a murine experimental autoimmune encephalomyelitis model [30]. A well-known soy component, isoflavones, reduce the oxidative stress in hippocampus in scopolamine-induced memory impairment mouse model [31].…”

Protective Efficacy of a Dietary Supplement Based on Forskolin, Homotaurine, Spearmint Extract, and Group B Vitamins in a Mouse Model of Optic Nerve Injury

“…Two weeks after ONC, RGC function was evaluated by measuring the PhNR as previously described [37]. Electroretinographic recordings were made using a Ganzfeld stimulator (Biomedica Mangoni, Pisa, Italy).…”

Inflammation in the anterior visual pathway in multiple sclerosis: what do the animal models teach us?

“…The neutralization of IL-17 completely prevented inner retinal layer thinning and immune cell infiltration, further underlining the importance of the IL-17-mediated pathway in EAE-ON [94,96] . In the early inflammatory phase of EAE, macrophages polarize towards a pro-inflammatory phenotype expressing increasing levels of pro-inflammatory markers such as CXCL-10, CXCL-11, IL-12 and IL-23 and thereby contributing to the influx of further inflammatory immune cells and cellular stress, whereas the percentage of anti-inflammatory macrophages is decreased [97] . A recent report suggested that fatty acids including omega-3 and omega-6 can promote a shift of macrophages towards the anti-inflammatory type by enhancing the phosphorylation of STAT3 and decreasing the phosphorylation of NF-kB [97] .…”

“…In the early inflammatory phase of EAE, macrophages polarize towards a pro-inflammatory phenotype expressing increasing levels of pro-inflammatory markers such as CXCL-10, CXCL-11, IL-12 and IL-23 and thereby contributing to the influx of further inflammatory immune cells and cellular stress, whereas the percentage of anti-inflammatory macrophages is decreased [97] . A recent report suggested that fatty acids including omega-3 and omega-6 can promote a shift of macrophages towards the anti-inflammatory type by enhancing the phosphorylation of STAT3 and decreasing the phosphorylation of NF-kB [97] . The anti-inflammatory phenotype is mainly characterized by the expression of the anti-inflammatory cytokine IL-10, which also independently showed the prevention of further microglial infiltration, MHC II expression and optic nerve demyelination [98] .…”