Abstract
Age-related macular degeneration (AMD) is characterized by the accumulation of debris in the posterior eye. In this study we evaluated peripheral blood monocyte phagocytic function at various stages of AMD and in aged matched control participants. Real-time tri-color flow cytometry was used to quantify phagocytic function of peripheral blood monocyte subsets (non-classic, intermediate and classic) isolated from subjects with intermediate or late AMD and compared with age matched healthy controls. Assessment of phagocytic function of monocytes isolated from those with and without reticular pseudodrusen was also made, and the effect of glatiramer acetate on phagocytic function assessed. Phagocytic function was reduced in all subjects with AMD, irrespective of stage of disease. However, there was no correlation between phagocytic function and drusen load, nor any difference between the level of phagocytosis in those with or without reticular pseudodrusen. Treatment with glatiramer acetate increased phagocytosis of classical and non-classical monocytes, normalizing the reduction in phagocytosis observed in those with AMD. These findings suggest that defective systemic phagocytosis is associated with both intermediate and late stages of AMD, highlighting a potential role in the accumulation of debris that occurs early in the disease process. Assessing peripheral monocyte phagocytic function provides further insights into the etiology of this disease and offer a novel therapeutic target.
Highlights
Age related macular degeneration (AMD) is the leading cause of irreversible vision loss in the western world [1]
The main findings of this study were that both intermediate and late Age-related macular degeneration (AMD) were associated with a reduction in monocyte phagocytosis that could be ameliorated in part by application of glatiramer acetate
The presence of reticular pseudodrusen (RPD) had no additional effect on monocyte phagocytosis compared to that observed in those without RPD
Summary
Age related macular degeneration (AMD) is the leading cause of irreversible vision loss in the western world [1]. Impaired Monocyte Phagocytosis in AMD by atrophic changes in the retina called geographic atrophy or aberrant vascular pathology called choroidal neovascularization [3, 4] Another distinct deposit seen clinically as reticular pseudodrusen (RPD), located between the RPE and photoreceptors, as sub retinal drusenoid deposits, has emerged and their importance highlighted in disease progression [5,6,7]. These different deposits, in combination with an accumulation of lipid rich deposits within Bruch’s membrane (BM), a semipermeable membrane located between the choroidal blood supply and the retina, are considered integral to the pathogenesis of AMD. In this study, we examined the in vitro effect of glatiramer acetate on phagocytic function in cells isolated from participants with AMD
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