Project Summary
Inflammation and in particular immune cells called macrophages and monocytes, are associated with all clinical stages of macular degeneration (AMD). How these immune cells contribute to progression of vision loss is unknown. With funding from BrightFocus Foundation, our lab is investigating the hypothesis that increased levels of a newly identified macrophage chemotactic factor correlates with progression and severity of AMD. Our study design calls for investigating the biological and physiological function of this chemotactic factor in cells that are vulnerable in AMD, including retinal pigment epithelial (RPE) cells that serve as nurse cells to the overlying retina; choroidal endothelial cells that stabilize the outer retinal vasculature; and monocytes, which are circulating immune cells capable of infiltrating and residing within the retinal tissue. Currently we are examining expression levels of this factor in eye tissue samples and blood serum from donor eyes with different stages of AMD. We are also determining the impact of this factor on the inflammatory state of macrophages. In other words, we are asking the question; Do high levels of this chemotactic factor induce a pro- or anti-inflammatory phenotype in macrophages? Finally, using mouse models, we are examining if high levels of this chemotactic factor can directly impact phenotypes characteristic of different clinical sub-types of AMD, including accumulation of sub-RPE deposits (drusen phenotype), and RPE cell loss (geographic atrophy phenotype). This study is the first to examine the role of this factor in AMD onset and progression utilizing a combination of cell culture models, mouse models, and human tissue samples. The results of these experiments will further clarify the contributions of this factor to AMD progression. Additionally by virtue of investigating its role in several AMD-vulnerable cells we will also be able to consider the therapeutic potential of this factor as a possible treatment for AMD.
