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Deficits in Monocyte Function in Age Related Macular Degeneration: A Novel Systemic Change Associated With the
Ben J Gu1,2, Xin Huang1, Pavan K Avula1
1The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
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.
Insights
Defective peripheral blood monocyte phagocytic function is linked to age-related macular degeneration (AMD). Glatiramer acetate treatment improved monocyte phagocytosis in AMD patients, suggesting a new therapeutic target.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Age-related macular degeneration (AMD) involves debris accumulation in the posterior eye.
- Systemic immune cell function may play a role in AMD pathogenesis.
Purpose of the Study:
- To evaluate peripheral blood monocyte phagocytic function in AMD patients.
- To investigate the effect of glatiramer acetate on monocyte phagocytosis in AMD.
Main Methods:
- Real-time tri-color flow cytometry was used to quantify phagocytic function.
- Monocyte subsets (non-classic, intermediate, classic) were analyzed from AMD patients and healthy controls.
- Phagocytic function was assessed in relation to drusen load and glatiramer acetate treatment.
Main Results:
- Phagocytic function was reduced in all AMD patients, regardless of disease stage.
- No correlation was found between phagocytic function and drusen load.
- Glatiramer acetate treatment enhanced phagocytosis in classical and non-classical monocytes, normalizing levels in AMD patients.
Conclusions:
- Defective systemic phagocytosis is associated with intermediate and late-stage AMD.
- Peripheral monocyte phagocytic function offers insights into AMD etiology.
- Modulating monocyte phagocytosis presents a potential therapeutic strategy for AMD.
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