Differential turnover rates of monocyte-derived cells in varied ocular tissue microenvironments

Jelena Kezic, Paul G McMenamin

Research output: Contribution to journalArticleResearchpeer-review

57 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)721 - 729
Number of pages9
JournalJournal of leukocyte biology
Volume84
Issue number3
DOIs
Publication statusPublished - 2008
Externally publishedYes

Cite this