Research Fellow University College London (UCL) London, England, United Kingdom
Abstract: Age-related macular degeneration (AMD) is a complex disease and the leading cause of blindness in the western world. During macular degeneration, retinal pigment epithelium (RPE) cells are lost due to stress and aging, resulting in damage to the retinal and in central vision loss. The immune system plays an important role in the development of AMD. Damage to the RPE triggers an immune response and chronic inflammation. Investigating the factors that lead to this local inflammation and immune response in AMD will contribute to a new understanding of AMD pathology, providing an opportunity to develop new treatments that could avoid vision loss in patients. Macrophages are immune cells that can promote inflammation and phagocytose foreign and unhealthy cells. Macrophages also play an important role in the aging process and the development of age-associated diseases, such as AMD. Samples from post-mortem tissue from AMD patients show an accumulation of macrophages around macular RPE, highlighting the importance of these cells in the development of AMD. In order to study macrophages characteristics, and behaviour, a stem cell-based AMD model system was developed. iPSC were generated from AMD, age-matched and young control patient samples, and iPSC were differentiated into macrophage subtypes (M0), and further differentiated into “proinflammatory” (M1) and anti-inflammatory (M2) subtypes. Immune-related gene and protein expression was examined by Q-PCR and Flow analysis, the secretome was assessed using cytokine arrays and functionality was tested by phagocytosis of bioparticles. Our data suggests that macrophage characteristics are altered in healthy ageing and disease. In the future, these cells will be used to study the activation of macrophages by inflammatory cytokines realised by RPE in vitro. This would help provide further understanding of the crosstalk between RPE and the immune system during the development of AMD.
