Deficits in Monocyte Function in Age Related Macular Degeneration: A Novel Systemic Change Associated With the Disease

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.

Glatiramer Acetate Immunomodulation: Evidence of Neuroprotection and Cognitive Preservation

“…The phenotypic heterogeneity of monocytes after GA immunization appeared to provide protection against drusen formation and reduced established total drusen area. Additionally, GA-mediated Th2 cells were shown to reduce retinal microglial cytotoxicity, likely induced by amyloid [24]. Another AMD study found a decrease in macular plaque formation [93].…”

“…Overall, GA promotes and improves phagocytic activity of monocytes and microglia towards myelin debris [13,22,23]. Thus, GA has been shown to impact the phenotype of myeloid cells, including monocytes and microglia, within the periphery and cerebral microenvironment [18,22,24,25].…”

“…Beyond RRMS, GA has become a proposed therapy for the treatment of age-related (adult-onset) macular degeneration (AMD) [24]. AMD is a degenerative disease that occurs when drusen, waste products from retinal rods and cones, accumulate over time in the macula causing changes in central and color vision [92].…”

“…AMD is a degenerative disease that occurs when drusen, waste products from retinal rods and cones, accumulate over time in the macula causing changes in central and color vision [92]. An animal model found that mice deficient in monocytes and/or macrophages developed hallmarks of AMD while a clinical trial similarly found a reduction in phagocytic activity in AMD patients [24,92]. Therefore, it was hypothesized that the depletion of monocytes and their phagocytic activity was part of the pathophysiological process of AMD.…”

“…All the studies that were reviewed displayed a positive correlation between GA administration and improvement in disease progression and/or clinical symptoms. [24] Participants in the treatment group of these studies were given GA 20 mg/s.c./qw (weekly); AMD: age-related macular degeneration; TDA: total drusen area; iAMD: intermediate adult-onset macular degeneration; lAMD: late adult-onset macular degeneration; IOP: intraocular pressure; RGC: retinal ganglion cell.…”