Role of Bona Fide Microglia in Retinal Degeneration

The deterioration of light-sensing nerves of the retina contributes to vision loss in patients with age-related macular degeneration (AMD). The immune system is thought to contribute to this deterioration, but how this is accomplished remains elusive. Our grant project seeks to identify the specific immune cell type that contributes to vision loss and to devise a strategy that neutralizes such cells to ultimately help preserve vision in patients suffering from age-related macular degeneration.

Understanding the role of the immune system in retinal degenerative diseases is an emerging and promising field in AMD research. Our project addresses a fundamental gap in this arena concerning the need to uncover the identity of specific immune cell types involved in this degenerative process, and to determine the factors that can be targeted therapeutically to possibly help preserve visual function in mouse models of AMD.

Our project is focused on a group of immune cells referred to as macrophages, which has caught the attention of researchers in the field. We are identifying a certain sub-type within the macrophage group that appears to be central to the aforementioned disease process. In parallel, we also are uncovering a unique factor necessary for this macrophage sub-type to function in the manner that it does in retinal degenerative disease. Thus, our experiments are testing whether targeting this factor is therapeutic in mice.

Our multi-disciplinary approach is one aspect that sets this project apart from the field. We implement the most cutting-edge understanding and tools available in macrophage research for these experiments. Specifically, we leverage a novel genetically-engineered mouse system, which enables us to both genetically manipulate these cells and “trace” their positions in the mouse disease setting.

The ultimate goal of these studies is to help reduce the burden of AMD in patients. Our project will significantly advance the current understanding of macrophages in retinal degeneration and possibly uncover new targets that may hold promise for helping to preserve vision in AMD patients.