title: Differential turnover rates of monocyte-derived cells in varied ocular tissue microenvironments.
abstract: Monocytes of bone marrow (BM) origin are circulating precursors that replenish dendritic cells and macrophage populations in peripheral tissues during homeostasis. The eye provides a unique range of varying tissue microenvironments in which to compare the different turnover rates of monocyte-derived cells. This was investigated in the present study using radiation chimeras, whereby BM from Cx3cr1(+/gfp) mice was used to rescue myeloablated wild-type (WT) BALB/c mice (conventional chimeras). The use of Cx3cr1(+/gfp) mice as BM donors allowed the clear visualization of newly recruited monocyte-derived cells. Following BM reconstitution, mice were killed at 2, 4, 6, and 8 weeks, and wholemount ocular tissues were processed for immunohistochemistry and confocal microscopy. "Reverse" chimeras (WT into Cx3cr1(+/gfp)) were also created to act as a further method of cross-referencing cell turnover rates. In conventional chimeras, Cx3cr1(+/gfp) cells began repopulating the uveal tract (iris, ciliary body, choroid) 2 weeks post-transplantation with close to complete replenishment by 8 weeks. By contrast, the earliest recruitment of Cx3cr1(+/gfp) cells into the host retina occurred at 4 weeks. In reverse chimeras, a steady accumulation of host Cx3cr1(+/gfp) macrophages in the subretinal space of Cx3cr1(+/gfp) adult mice suggests that these cells arise from long-term resident microglia and not newly recruited WT donor cells. In summary, chimeric mouse models, in which lineage-specific cells carry a fluorescent reporter, have been used in the present study to visualize the turnover of monocyte-derived cells in different tissue compartments of the eye. These data provide valuable insights into differential monocyte turnover rates within a single complex organ.
authors.affiliation: School of Anatomy and Human Biology, The University of Western Australia, Perth, Western Australia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Kezic
authors.forename: Paul G
authors.initials: PG
authors.lastname: McMenamin
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D000073883:CX3C Chemokine Receptor 1; D019070:Cell Lineage; D002924:Ciliary Body / Q000166:cytology / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology; D005123:Eye / Q000166:cytology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007498:Iris / Q000166:cytology / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D011828:Radiation Chimera; D019707:Receptors, Chemokine / Q000502:physiology*; D012160:Retina / Q000166:cytology*; D014602:Uvea / Q000166:cytology / Q000502:physiology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins