Abstract
Presentation Description :
Macrophages in adult physiological conditions are the most abundant, have the longest lifespan, and arguably are the most functionally diverse cell population of the mononuclear phagocyte system. Unlike their neighboring dendritic cells, for example, which mainly serve in antigen presentation, macrophages have major non-immunological roles throughout the mammalian organism, such as in thermoregulation, peristalsis, and synaptic pruning. Underscoring their functional significance, deletion of Csf1r is postnatally lethal in mice, and this significance is evolutionarily conserved as deficiencies of this gene in humans can likewise cause neurologic, osteologic, and oncologic disease. A central factor that underpins the functional specialization of macrophages is their developmental origins, which is generally binary. One set of origins comes from “primitive” hematopoiesis, in which these macrophages are established from prenatal seeding and subsequently maintained throughout adulthood via their exceedingly long lifespans and self-renewability. The second origin comes from “definitive” hematopoiesis, in which these macrophages are transient in the adult setting and maintained via persistent turnover from circulating monocytes. The predominance of a macrophage lineage in each tissue is largely dependent on the accessibility of circulating monocytes. Congruent with this model in the mouse eye, we showed that choroidal macrophages are “definitively” derived, which is consistent with a high monocyte access due to the fenestrated choriocapillaris. The converse is also true in the mouse eye, as we showed that retinal macrophages (i.e., microglia) are “primitively” derived, which is consistent with limited monocyte access due to the blood-retinal barrier. Intriguingly, work from our lab is showing that the avascular cornea represents a unique exception to this binary model, raising new questions in macrophage ontogeny and their role in corneal physiology, which will be the focus of my talk.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.