Efficacy of a Fatty Acids Dietary Supplement in a Polyethylene Glycol-Induced Mouse Model of Retinal Degeneration

Abstract

Current knowledge of the benefits of nutrition supplements for eye pathologies is based largely on the use of appropriate animal models, together with defined dietary supplementation. Here, C57BL6 mice were subretinally injected with polyethylene glycol (PEG)-400, an established model of retinal degeneration with a dry age-related macular degeneration (AMD)-like phenotype, an eye pathology that lacks treatment. In response to PEG-400, markers of the complement system, angiogenesis, inflammation, gliosis, and macrophage infiltration were upregulated in both retinas and retinal pigment epithelium (RPE)/choroids, whereas dietary supplementation with a mixture based on fatty acids counteracted their upregulation. Major effects include a reduction of inflammation, in both retinas and RPE/choroids, and an inhibition of macrophage infiltration in the choroid, yet not in the retina, suggesting a targeted action through the choroidal vasculature. Histological analysis revealed a thinning of the outer nuclear layer (ONL), together with dysregulation of the epithelium layer in response to PEG-400. In addition, immunohistofluorescence demonstrated Müller cell gliosis and macrophage infiltration into subretinal tissues supporting the molecular findings. Reduced ONL thickness, gliosis, and macrophage infiltration were counteracted by the diet supplement. The present data suggest that fatty acids may represent a useful form of diet supplementation to prevent or limit the progression of dry AMD.

TRPV4 inhibition prevents increased water diffusion and blood-retina barrier breakdown in the retina of streptozotocin-induced diabetic mice

“…The present data show the retina as a single MR-detected layer, as previously reported (Berkowitz et al, 2004; Roberts et al, 2003). Our MRI estimation of total retinal thickness in control wt mice (275.5 ± 6.1 μm) compares reasonably well with our own values using histology (278.7 ± 2.6 μm) and also with published values using histology, anatomical MRI and OCT from the same mouse strain (270.4 ± 2.3 μm (Cammalleri et al, 2017), 237 ± 3 μm (Berkowitz et al, 2015) and 222.3 ± 2.1 μm (Dysli et al, 2015), respectively). This, however, does not stand true in diabetic mice, where MRI-based measurements showed retinal thinning and histological ones did not.…”

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

“…Gangliomix (200 µL of the suspension) was administered by oral gavage for 14 days before and 14 days after ONC. Although not allowing to discriminate between preventive and curative efficacy, this regimen is supported by previous findings in a mouse model of dry AMD, in which fatty acids supplementation after the model was established, was nearly inferior (however, not nihil) to the preand post-supplementation [36]. In this respect, food supplements cannot be intended as therapeutic agents to be taken to treat a certain pathology, but they are used to integrate the normal diet with elements that are not present in a sufficient amount.…”

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

“…It is known that both omega-3 and omega-6 FAs may be converted by several cell populations in bioactive lipids, which mediate the end of an inflammatory response thus preventing the occurrence of a pathological chronic inflammation (see [ 57 ]). In this respect, we have previously demonstrated in a mouse model of dry age-related macular degeneration, characterized by a strong inflammatory component leading to retinal thinning, that a patented diet supplement composed by omega-3 and omega-6 FAs, lycopene and spirulina reduces inflammation and prevents retinal degeneration [ 21 ]. In addition, the finding that nFAG reduces inflammation and gliosis without interfering with macrophage infiltration and the related OCM production may be beneficial since infiltrating macrophages are a known source of trophic and growth factors [ 58 ].…”

“…Among the different mixtures, an orally-administered compound based on FAG with the addition of lycopene and spirulina, designated as Macular-FAG (mFAG ® ), is commercialized by Sooft Italia SpA (Montegiorgio, Italy) with a main recommendation for patients with early signs of atrophic macular degeneration. Indeed, a recent study demonstrated that mFAG is able to limit the acute inflammatory reaction and macrophage infiltration triggered by a drusen-like insult in a mouse model of dry AMD [ 21 ] thus opening the way for further investigations using FAG in inflammatory diseases of the eye. An additional FAG-based compound, designated as Neuro-FAG (nFAG ® ), contains a different mix of FAs in different proportions, plus lycopene, and has been developed to specifically treat inflammatory events damaging RGCs and their axons.…”