Macrophage Origin and Function during Experimental Wet Macular Degeneration
MentorHarris R. Perlman, PhD
We will determine how microglia, classical, and non-classical monocyte-derived macrophages influence new blood vessel growth during a spontaneous model of experimental wet macular degeneration. In Specific Aim 1, we will show that classical monocyte-derived macrophages stimulate new blood vessel growth, identify subtypes of classical monocyte-derived macrophages, and determine which subtype promotes new blood vessel growth. In Specific Aim 2, we will demonstrate that non-classical monocyte-derived macrophages inhibit new blood vessel growth, determine which macrophage subsets are derived from non-classical monocyte-derived macrophages, and identify the role of microglia in new blood vessel growth.
Our studies are unique because we use advanced methods in a spontaneous wet macular degeneration model. We will perform a multiparameter flow cytometry panel for 10-20 color discrimination, which will allow us to identify macrophage subsets in a highly specific manner. In addition, we use state-of-the-art double hit mouse models to deplete macrophage subtypes specifically. These techniques will determine the mechanism by which different macrophage subsets stimulate new blood vessel growth during experimental wet macular degeneration. Our study is designed to detect macrophage subtypes that either increase or decrease blood vessel growth during wet macular degeneration. These results could translate into macrophage subset therapy. Cell-based therapies are advantageous over single-molecule therapies because they can target multiple pathways by which macrophages influence new blood vessel growth. By identifying unique markers for macrophage subsets, therapeutics can be designed to either deplete blood vessel activating macrophages or stimulate blood vessel inhibiting macrophage subtypes.