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Yikui Zhang, Lian Zhao, Xu Wang, Robert N Fariss, Wai T Wong; Repopulation of the retina by myeloid cells following depletion of endogenous retinal microglia in adult mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4185.
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© ARVO (1962-2015); The Authors (2016-present)
Microglia, the resident population of immune cells in the retina, represent a long-lived population of cells that tile the entire retina in an uniform and regular pattern. The factors that maintain microglial homeostasis in terms of their presence and distribution in the retina are not known. We investigate myeloid cell homeostasis in the retina following acute depletion of microglia and characterize the distribution and nature of repopulating myeloid cells.
Microglia were depleted in young, 2-month old CX3CR1CreER; Rosa26-flox-STOP-flox-DTA transgenic mice by inducing a microglial-specific expression of diphtheria toxin subunit alpha by tamoxifen administration. The repopulation of the retina by Iba1+ myeloid cells was monitored by immunohistochemistry at time-points up to 5 months following depletion.
Following short-term acute depletion of endogenous retinal microglia (>95%), Iba1+ myeloid cells were observed to repopulate the retina beginning at Day 9 after depletion. These cells emerged predominantly in the peripapillary region and demonstrated rounded or amoeboid morphologies and stained positively for isolectin IB4 , F4/80, and CD68. Repopulating cells extended progressively from center to periphery, acquiring an increasingly more ramified morphology with time. Repopulating cells appear targeted initially to the IPL and then the OPL, spacing themselves out in a horizontal mosaic distribution, resembling that observed in endogenous microglia. Repopulating cells can be found extending to all retinal areas by 1 month but full recovery of microglial densities in the IPL and OPL was slow, requiring up to 5 months.
Homeostatic mechanisms exist in the retina to induce a repopulation by myeloid cells following microglial depletion. Guidance cues appear to be present to guide repopulating cells to the correct retinal lamina and to re-establish a mosaic distribution of ramified, non-overlapping cells. Current work is focused on understanding the mechanisms for microglial homeostasis and the functional implications of myeloid cell repopulation in the retina.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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