Research Areas/Projects
Macrophage heterogeneity in the laser-induced model of neovascular AMD
The laser-induced CNV model uses a laser injury to create a new blood vessels growth in the back of the eye that models neovascular AMD. Prior studies by our lab, and others, have shown that infiltrating macrophages from blood monocytes are key cells for this process. Using single-cell RNA-sequencing, we showed that a population of CD11c+ macrophages that comes from the blood monocytes expresses a number of genes that stimulate new blood vessel growth. Furthermore, we depleted CD11c+ macrophages using a genetic model and reduced the size of these laser-induced new blood vessel growths. Our future studies seek to understand more deeply the mechanism by which CD11c+ macrophages stimulate new blood vessel growth.
Macrophage heterogeneity in spontaneous model of neovascular AMD
The Vldlr-knockout mouse develops spontaneous new blood vessel growths in the back of the eye between the retina and choroid. Prior work, which we have replicated, shows that global macrophage depletion severely reduces the size of these new blood vessel growths. Our goal is to understand which macrophages are key for this process and how they stimulate new blood vessel growth. We have found that monocyte-derived macrophages are not necessary for this model, which is in contrast to the laser-induced model. Our current goal is to understand whether this process is driven by microglia that migrate from the retina to these lesions in the subretinal space or choroidal macrophages that migrate from the choroid into the sub-retinal space.
Role of perivascular macrophages in homeostasis and disease
Perivascular macrophages are macrophages that exist on blood vessels in the retina. In the brain, we know that these cells are important for blood-brain barrier homeostasis, but almost nothing is known about these cells in the retina. We have so far identified that these cells are the second most common macrophage in the retina, exist on small veins, express unique marker genes compared to retinal microglia, and are associated with infiltrating inflammatory cells. We are currently investigating if depleting perivascular macrophages will result in a dysregulation of the blood-brain barrier and if inflammatory infiltration will be affected.
