Abstract
Purpose :
Atrophic Age-Related Macular Degeneration (AMD) is characterized by the presence of insoluble residues (drusen) between the RPE and the Bruch’s membrane. Such atrophic disease may progress towards geographic atrophy (90% of the cases), or choroid neovascularization (CNV: 10% of the cases). The neovascular form can be treated by anti-VEGF therapy, but no satisfactory treatment exists for the atrophic disease. Aim of this work has been to investigate in a murine model of the atrophic form the efficacy of an innovative food supplement orally administered during the course of the disease.
Methods :
We used a murine model in which a subretinic injection of polyethylene glycol 400 (PEG: 0.5 mg in 2 ml) simulates the occurrence of drusen, and starts an inflammatory degenerative reaction simulating an acute development of atrophic AMD (Lyzogubov et al., 2014). A mixture (10 mg in 0.2 ml) of fatty acids, palmitoyl-ethanolamide, lycopene and spirulin (mFAG) diluted in sugar-water has been given by daily gavage to animals fed with a standard diet, starting 10 days before the insult and continuing up to 5 days after PEG injection. Control animals received gavage treatment with sugar-water only. Molecular markers of inflammation, glia activation and macrophage infiltration have been investigated in the retina and the choroid separately by mRNA and protein expression.
Results :
Six days after PEG injection there was a significant increase in inflammatory (TNFa, IL1b, IL6, IL7 and IL8), glia activation (GFAP, ICAM1 and iNOS) and macrophage infiltration (CD68 and F4/80) markers at the mRNA level in the retina and the choroid. The increase in macrophage infiltration was confirmed at the protein level by ELISA. Oral treatment with mFAG, but not with the vehicle alone, resulted in a significant reduction of all these markers (however, not at baseline levels) in the retina and the choroid, with the only exception of macrophage infiltration, which was decreased in the choroid, but not in the retina.
Conclusions :
Our data show that oral administration of such innovative food supplement is able to limit the acute inflammatory reaction and the macrophage infiltration triggered by a drusen-like insult. Therefore, it might be a useful tool to prevent or limit the progression of atrophic AMD to CNV in humans. Clinical studies are now running to confirm the observed effects in early AMD patients.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.